A Phase 3 interventional study of Pitavastatin and Placebo in HIV and Cardiovascular Diseases, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 137 sites in 13 countries. Open to participants aged 40 Years to 75 Years. Per ClinicalTrials.gov, last updated 2025-09-04.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 3, Interventional, and Prevention
People with HIV are at risk for cardiovascular disease (CVD). This study evaluated the use of pitavastatin to reduce the risk of CVD in adults with HIV on antiretroviral therapy (ART).
The REPRIEVE trial consisted of two parallel identical protocols:
There are few strategies to prevent CVD in people with HIV (PWH), even though they are at high risk for developing CVD. Statin medications are used to lower cholesterol and may be effective at reducing the risk of CVD in PWH. The purpose of this study was to evaluate the use of pitavastatin to reduce the risk of CVD in PWH on ART.
This study enrolled PWH who were on any ART regimen (ART was not provided by the study) for at least 6 months before study entry and were at low to moderate risk of CVD using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline thresholds for recommended statin initiation.
Participants were randomly assigned to receive 4 mg of pitavastatin or placebo once a day for their entire study duration. Pitavastatin or placebo could be discontinued and clinically indicated statin therapy initiated at the discretion of the site investigator or the participant's care provider, with the intention of following the participant according to the intention-to-treat trial design. Study visits occurred at study entry and Months 1 and 4. Starting at Month 4, study visits occurred every 4 months for the rest of the study. Depending on when participants enrolled, they were in the study for a total of 4 to 8 years. Study visits included medical and medication history reviews, physical examinations, blood collections, assessments and questionnaires, urine collections (for some participants), and an electrocardiogram (ECG) (at study entry only).
Participants at US sites had the option of enrolling in a substudy (Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers: Mechanistic Substudy of REPRIEVE [A5333s]). The substudy evaluated the effect of pitavastatin on the progression of non-calcified coronary atherosclerotic plaque (NCP) and inflammatory biomarkers in PWH. Participants in the substudy attended study visits at study entry and Months 4 and 24. The visits included questionnaires and assessments, a blood collection, and a coronary computed tomography angiography (CCTA). The Mechanistic Substudy closed to accrual on February 6, 2018, when its accrual target of 800 participants had been reached. Sites that enrolled participants into the Mechanistic Substudy are indicated with asterisk (*) at the end of the institution names in the Contacts and Locations section.
Participants enrolled in REPRIEVE from select study sites, including international sites, through December, 2017, were included in the REPRIEVE Kidney Function Objectives Cohort to evaluate the effects of pitavastatin on parameters of kidney function in the setting of HIV. These objectives include evaluating high risk groups and mechanisms driving kidney function decline in the setting of HIV.
Women and men enrolled in REPRIEVE after February, 2016 were included in an observational cohort (REPRIEVE Women's Objectives Cohort) facilitating assessment of sex-specific mechanisms of CVD risk and risk reduction among PWH. This effort also included an evidence-based recruitment campaign to enhance women's participation in REPRIEVE.
In response to the SARS-CoV-2 pandemic, a supplemental objective was added in 2020. To better understand how COVID-19 affects PWH and if pitavastatin may reduce the risk of serious COVID-19 disease, we evaluated interrelated but independent key topics including epidemiology, host factors, and protective strategies. Starting from April 2020, COVID-19 assessment was completed at each study visit, and blood was collected for COVID-19 biomarkers.
The data and safety monitoring board (DSMB) recommended stopping the trial for efficacy at the second planned review on March 30, 2023, and concluded that no unexpected safety concerns had been reported. Following the DSMB action, participants were asked to return for the final study visit. All final visits were completed by August 21, 2023. We here present the results based on the final trial database, including the full follow-up out to closeout visits.
5,368 studies on the registry are indexed under Cardiovascular Diseases; 939 are open to participants now.
This study's enrollment of 7,769 is above the median of 100 across 3,084 interventional studies indexed under Cardiovascular Diseases.
Browse Cardiovascular Diseases studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Acceptable screening laboratories including:
Fasting low-density lipoprotein (LDL) cholesterol as follows:
Exclusion Criteria:
Clinical ASCVD, as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CD4 count
The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants received pitavastatin once a day for the entire time they were in study follow-up.
Drug: Pitavastatin
Participants received placebo for pitavastatin once a day for the entire time they were in study follow-up.
Drug: Placebo
One tablet (4 mg) taken once daily, orally with or without food
One tablet taken once daily, orally with or without food
Incidence Rate of Major Adverse Cardiovascular Event (MACE)
MACE is a composite of cardiovascular (CV) death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack (TIA), peripheral arterial ischemia, coronary, carotid or peripheral arterial revascularization, or death from an undetermined cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Cardiac Ischemia or Myocardial Infarction
Cardiac ischemia or myocardial infarction component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Cerebrovascular Event (Stroke or TIA)
Cerebrovascular event (stroke or TIA) component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Peripheral Arterial Ischemia
Peripheral arterial ischemia component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death From CV Causes
CV death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths and deaths from undetermined causes were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death From CV or Undetermined Causes
CV or undetermined death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Cardiac Catheterization or Revascularization
Cardiac cardiac catheterization or revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Carotid or Cerebrovascular Revascularization
Carotid or cerebrovascular revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Peripheral Arterial Revascularization
Peripheral arterial revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of MACE or Death
A composite outcome including MACE and death from any cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Death (All-cause)
Death from any cause. The incidence rates were estimated based on time to event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-CV Clinical Diagnoses
A composite of non-CV clinical diagnoses including: non-AIDS-defining cancers (excluding basal cell and squamous cell carcinomas of the skin), AIDS-defining events (based on Centers for Disease Control and Prevention \[CDC\] 2014 classification), end-stage renal disease, and end-stage liver disease. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-AIDS-defining Cancer
Non-AIDS-defining cancer (excluding basal cell and squamous cell carcinomas of the skin) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of AIDS-defining Event
AIDS-defining event component of the composite non-CV clinical diagnoses outcome. Events were captured based on the Centers for Disease Control and Prevention \[CDC\] 2014 classification. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of End-Stage Renal Disease
End-stage renal disease (defined as initiation of dialysis or renal transplantation) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of End-Stage Liver Disease
End-stage liver disease (defined as cirrhosis or hepatic decompensation requiring hospitalization) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Non-fatal Serious Adverse Event
Safety analysis outcome measure of non-fatal serious adverse event was defined by International Conference on Harmonisation (ICH) criteria. Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Diabetes
Safety analysis outcome measure of diabetes was defined as new diagnosis of diabetes with initiation of anti-diabetic agent. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Myalgia, Muscle Weakness or Myopathy
Safety analysis outcome measure of myalgia, muscle weakness or myopathy which were grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Rhabdomyolysis
Safety analysis outcome measure of rhabdomyolysis which was grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Grade 3 or Higher ALT
Safety analysis outcome measure of Grade 3 or higher alanine transaminase (ALT). Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of Adverse Event (AE)
Safety analysis outcome measure of any AE. AE collection included events of grade ≥3, those that were serious (defined by International Conference on Harmonisation (ICH) criteria) or treatment-limiting, and targeted diagnosis of diabetes. Grade ≥3 includes events that were grade 3 (serious) or grade 4 (life-threatening) per DAIDS AE Grading Table (version 2.1). Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Fasting Low-density Lipoprotein Cholesterol (LDL-C)
LDL-C level was derived as LDL-C calculated according to the Friedewald formula at triglycerides ≤400 mg/dL, and direct LDL-C at triglycerides \>400 to \<500 mg/dL. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: At entry and months 12, 24, 36, 48, 60, 72, 84. Participants' follow-up time on study varied, depending on their time of enrollment.
Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Non-HDL cholesterol levels were calculated as total cholesterol minus HDL cholesterol. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: At entry and months 12, 24, 36, 48, 60, 72, 84. Participants' follow-up time on study varied, depending on their time of enrollment.
Incidence Rate of Serious COVID-19
Serious COVID-19 was defined as COVID-19 that resulted in hospitalization or death or was life-threatening as per the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline E2A definition. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From January 1, 2020 through end of study; the median follow-up time was 3.3 years.
Incidence Rate of COVID-19
COVID-19 was defined as COVID-19 clinical diagnosis or positive test result (SARS-CoV-2 PCR or rapid antigen tests). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios (prescribed pitavastatin compared to placebo) from Poisson regression models, adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: From January 1, 2020 through end of study; the median follow-up time was 3.3 years.
For Mechanistic Substudy: Change in Non-Calcified Plaque (NCP) Volume From Baseline to Year 2
NCP was defined as plaque voxels with attenuation of \<350. Change in NCP is expressed as absolute change from baseline (calculated as NCP volume at 2 years minus NCP volume at entry), based on quantitative read of the CT scan, whenever available. Participants without a quantitative read and no evidence of NCP based on the corresponding qualitative read were assigned a value of zero for the change. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and Year 2.
For Mechanistic Substudy: Number of Participants With Progression of NCP From Baseline to Year 2
Progression at Year 2 was defined as any progression/increase in NCP volume in participants with evidence of NCP at entry, or incident NCP in participants without evidence of NCP at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and year 2.
For Mechanistic Substudy: Change in Total Plaque Volume From Baseline to Year 2
Total plaque includes all plaque voxels (noncalcified + calcified). Change in total plaque volume is expressed as absolute change from baseline (calculated as volume at 2 years minus volume at entry). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and year 2.
For Mechanistic Substudy: LpPLA2 Level
Level of inflammatory biomarker lipoprotein-associated phospholipase A2 (LpPLA2). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
For Mechanistic Substudy: Change in LpPLA2 From Baseline
Change in inflammatory biomarker LpPLA2 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
For Mechanistic Substudy: HsCRP Level
Level of inflammatory marker high-sensitivity C-reactive protein (HsCRP). Censored values below or above the assay limit were imputed. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
For Mechanistic Substudy: Change in HsCRP From Baseline
Change in inflammatory biomarker hsCRP from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
For Mechanistic Substudy: Soluble CD163 Level
Level of immune biomarker soluble CD163. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
For Mechanistic Substudy: Change in Soluble CD163 From Baseline
Change in immune biomarker soluble CD163 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
Time frame: Entry and month 24.
Incidence Rate of MACE by Sex
Subgroup analysis of the primary composite MACE outcome measure (as described above) by sex. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include sex and interaction of sex and treatment, to evaluate modification of statin effect.
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Incidence Rate of MACE by Race
Subgroup analysis of the primary composite MACE outcome measure (as described above) by race. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include race and interaction of race and treatment, to evaluate modification of statin effect.
Time frame: From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).
Participants were enrolled from March 26, 2015 to July 31, 2019.
| Milestone | Pitavastatin | Placebo |
|---|---|---|
| Started | 3888 | 3881 |
| Enrolled in mechanistic substudy | 402 | 402 |
| Completed mechanistic substudy | 349 | 350 |
| Completed | 3201 | 3201 |
| Not completed | 687 | 680 |
| Withdrew: Withdrawal by subject | 315 | 324 |
| Withdrew: Lost to follow-up | 258 | 249 |
| Withdrew: Unable to get to clinic | 69 | 60 |
| Withdrew: Physician decision | 25 | 25 |
| Withdrew: Site closure | 15 | 19 |
| Withdrew: Other | 5 | 3 |
MACE is a composite of cardiovascular (CV) death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack (TIA), peripheral arterial ischemia, coronary, carotid or peripheral arterial revascularization, or death from an undetermined cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Major Adverse Cardiovascular Event (MACE) | 4.95 (4.07 to 6.03) | 7.77 (6.64 to 9.08) |
Cardiac ischemia or myocardial infarction component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Cardiac Ischemia or Myocardial Infarction | 1.48 (1.03 to 2.11) | 2.65 (2.03 to 3.46) |
Cerebrovascular event (stroke or TIA) component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Cerebrovascular Event (Stroke or TIA) | 1.53 (1.07 to 2.17) | 2.46 (1.86 to 3.24) |
Peripheral arterial ischemia component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Peripheral Arterial Ischemia | 0.10 (0.02 to 0.39) | 0.15 (0.05 to 0.45) |
CV death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths and deaths from undetermined causes were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Death From CV Causes | 0.69 (0.41 to 1.16) | 0.98 (0.63 to 1.51) |
CV or undetermined death component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Non-CV deaths were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Death From CV or Undetermined Causes | 1.72 (1.23 to 2.39) | 2.54 (1.94 to 3.33) |
Cardiac cardiac catheterization or revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Cardiac Catheterization or Revascularization | 1.08 (0.71 to 1.64) | 1.77 (1.27 to 2.45) |
Carotid or cerebrovascular revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Carotid or Cerebrovascular Revascularization | 0 (NA to NA) | 0 (NA to NA) |
Peripheral arterial revascularization component of the primary composite MACE outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Peripheral Arterial Revascularization | 0 (NA to NA) | 0.29 (0.13 to 0.65) |
A composite outcome including MACE and death from any cause. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of MACE or Death | 9.31 (8.07 to 10.75) | 12.02 (10.60 to 13.63) |
Death from any cause. The incidence rates were estimated based on time to event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Death (All-cause) | 6.18 (5.19 to 7.36) | 6.99 (5.93 to 8.23) |
A composite of non-CV clinical diagnoses including: non-AIDS-defining cancers (excluding basal cell and squamous cell carcinomas of the skin), AIDS-defining events (based on Centers for Disease Control and Prevention \[CDC\] 2014 classification), end-stage renal disease, and end-stage liver disease. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Non-CV Clinical Diagnoses | 9.17 (7.93 to 10.59) | 9.90 (8.61 to 11.38) |
Non-AIDS-defining cancer (excluding basal cell and squamous cell carcinomas of the skin) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Non-AIDS-defining Cancer | 5.25 (4.34 to 6.36) | 5.68 (4.74 to 6.83) |
AIDS-defining event component of the composite non-CV clinical diagnoses outcome. Events were captured based on the Centers for Disease Control and Prevention \[CDC\] 2014 classification. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of AIDS-defining Event | 3.36 (2.65 to 4.27) | 3.55 (2.82 to 4.47) |
End-stage renal disease (defined as initiation of dialysis or renal transplantation) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of End-Stage Renal Disease | 0.15 (0.05 to 0.46) | 0.24 (0.10 to 0.59) |
End-stage liver disease (defined as cirrhosis or hepatic decompensation requiring hospitalization) component of the composite non-CV clinical diagnoses outcome. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated via cause-specific relative hazard (i.e. hazard ratio) of prescribed pitavastatin compared to placebo from Cox proportional hazards models, stratified by screening CD4 count and sex. Deaths (without preceding event of interest) were treated as competing events and censored. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of End-Stage Liver Disease | 0.59 (0.33 to 1.04) | 0.64 (0.37 to 1.10) |
Safety analysis outcome measure of non-fatal serious adverse event was defined by International Conference on Harmonisation (ICH) criteria. Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Non-fatal Serious Adverse Event | 4.17 (3.88 to 4.48) | 4.18 (3.89 to 4.49) |
Safety analysis outcome measure of diabetes was defined as new diagnosis of diabetes with initiation of anti-diabetic agent. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Diabetes | 1.18 (1.04 to 1.34) | 0.91 (0.79 to 1.06) |
Safety analysis outcome measure of myalgia, muscle weakness or myopathy which were grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Myalgia, Muscle Weakness or Myopathy | 0.46 (0.38 to 0.56) | 0.29 (0.23 to 0.38) |
Safety analysis outcome measure of rhabdomyolysis which was grade 3 or higher or treatment-limiting. Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Rhabdomyolysis | 0.015 (0.005 to 0.046) | 0.020 (0.007 to 0.052) |
Safety analysis outcome measure of Grade 3 or higher alanine transaminase (ALT). Grade 3 or higher includes grade 3 and 4 events, where grade 3 refers to severe and grade 4 to life-threatening, according to DAIDS AE Grading Table (version 2.1). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo). Due to small number of events, there was no adjustment for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Grade 3 or Higher ALT | 0.059 (0.033 to 0.10) | 0.044 (0.023 to 0.085) |
Safety analysis outcome measure of any AE. AE collection included events of grade ≥3, those that were serious (defined by International Conference on Harmonisation (ICH) criteria) or treatment-limiting, and targeted diagnosis of diabetes. Grade ≥3 includes events that were grade 3 (serious) or grade 4 (life-threatening) per DAIDS AE Grading Table (version 2.1). Fatal events were excluded as deaths were a secondary efficacy outcome (see outcome measure: incidence rate of death (all-cause)). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for screening CD4 and sex. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Adverse Event (AE) | 8.83 (8.38 to 9.31) | 8.49 (8.05 to 8.95) |
LDL-C level was derived as LDL-C calculated according to the Friedewald formula at triglycerides ≤400 mg/dL, and direct LDL-C at triglycerides \>400 to \<500 mg/dL. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mg/dL | Pitavastatin | Placebo |
|---|---|---|
| Entry: LDL-C | 107 (87 to 129) | 106 (86 to 127) |
| Month 12: LDL-C | 74 (58 to 92) | 105 (85 to 126) |
| Month 24: LDL-C | 75 (59 to 93) | 104 (84 to 126) |
| Month 36: LDL-C | 73 (57 to 92) | 104 (83 to 126) |
| Month 48: LDL-C | 73 (56 to 92) | 103 (83 to 124) |
| Month 60: LDL-C | 73 (56 to 93) | 103 (82 to 125) |
| Month 72: LDL-C | 74 (57 to 95) | 101 (82 to 122) |
| Month 84: LDL-C | 75 (59 to 98) | 98 (81 to 121) |
Non-HDL cholesterol levels were calculated as total cholesterol minus HDL cholesterol. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mg/dL | Pitavastatin | Placebo |
|---|---|---|
| Entry: non-HDL-C | 133 (110 to 158) | 132 (108 to 157) |
| Month 12: non-HDL-C | 97 (80 to 118) | 131 (108 to 156) |
| Month 24: non-HDL-C | 98 (80 to 121) | 131 (108 to 156) |
| Month 36: non-HDL-C | 97 (78 to 118) | 130 (107 to 154) |
| Month 48: non-HDL-C | 96 (77 to 119) | 128 (106 to 154) |
| Month 60: non-HDL-C | 96 (78 to 120) | 127 (104 to 153) |
| Month 72: non-HDL-C | 95 (78 to 121) | 124 (104 to 150) |
| Month 84: non-HDL-C | 99 (80 to 124) | 123 (101 to 151) |
Serious COVID-19 was defined as COVID-19 that resulted in hospitalization or death or was life-threatening as per the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Guideline E2A definition. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios from Poisson regression models (prescribed pitavastatin compared to placebo), adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of Serious COVID-19 | 0.45 (0.34 to 0.59) | 0.60 (0.48 to 0.77) |
COVID-19 was defined as COVID-19 clinical diagnosis or positive test result (SARS-CoV-2 PCR or rapid antigen tests). The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The treatment effect was estimated using incidence rate ratios (prescribed pitavastatin compared to placebo) from Poisson regression models, adjusted for GBD region to account for regional differences. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| events per 100 person-years | Pitavastatin | Placebo |
|---|---|---|
| Incidence Rate of COVID-19 | 8.79 (8.22 to 9.39) | 8.35 (7.80 to 8.93) |
NCP was defined as plaque voxels with attenuation of \<350. Change in NCP is expressed as absolute change from baseline (calculated as NCP volume at 2 years minus NCP volume at entry), based on quantitative read of the CT scan, whenever available. Participants without a quantitative read and no evidence of NCP based on the corresponding qualitative read were assigned a value of zero for the change. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mm^3 | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Change in Non-Calcified Plaque (NCP) Volume From Baseline to Year 2 | -1.70 ± 25.2 | 2.62 ± 27.1 |
Progression at Year 2 was defined as any progression/increase in NCP volume in participants with evidence of NCP at entry, or incident NCP in participants without evidence of NCP at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| Participants | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Number of Participants With Progression of NCP From Baseline to Year 2 | 53 | 85 |
Total plaque includes all plaque voxels (noncalcified + calcified). Change in total plaque volume is expressed as absolute change from baseline (calculated as volume at 2 years minus volume at entry). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mm^3 | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Change in Total Plaque Volume From Baseline to Year 2 | 2.34 ± 28.7 | 6.89 ± 32.3 |
Level of inflammatory biomarker lipoprotein-associated phospholipase A2 (LpPLA2). Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| ng/mL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| Entry | 126 (94.8 to 169) | 131 (89.6 to 163) |
| Month 24 | 119 (84.0 to 160) | 143 (105 to 186) |
Change in inflammatory biomarker LpPLA2 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| ng/mL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Change in LpPLA2 From Baseline | -9.77 (-33.6 to 16.8) | 19.9 (-5.6 to 43.0) |
Level of inflammatory marker high-sensitivity C-reactive protein (HsCRP). Censored values below or above the assay limit were imputed. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mg/dL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| Entry | 0.18 (0.08 to 0.39) | 0.18 (0.09 to 0.33) |
| Month 24 | 0.17 (0.07 to 0.36) | 0.19 (0.10 to 0.40) |
Change in inflammatory biomarker hsCRP from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| mg/mL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Change in HsCRP From Baseline | -0.01 (-0.10 to 0.08) | 0.01 (-0.09 to 0.11) |
Level of immune biomarker soluble CD163. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| ng/mL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| Entry | 849 (651 to 1163) | 845 (613 to 1074) |
| Month 24 | 1013 (728 to 1419) | 1003 (745 to 1384) |
Change in immune biomarker soluble CD163 from baseline calculated as value at month 24 minus value at entry. Treatment discontinuation was ignored, including the initiation of statin therapy as part of clinical care (intention to treat policy).
| ng/mL | Pitavastatin (Substudy) | Placebo (Substudy) |
|---|---|---|
| For Mechanistic Substudy: Change in Soluble CD163 From Baseline | 149 (-60.8 to 420) | 143 (-46.0 to 453) |
Subgroup analysis of the primary composite MACE outcome measure (as described above) by sex. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include sex and interaction of sex and treatment, to evaluate modification of statin effect.
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Among females | 3.9 (2.7 to 5.8) | 6.2 (4.6 to 8.4) |
| Among males | 5.5 (4.4 to 6.9) | 8.5 (7.1 to 10.2) |
Subgroup analysis of the primary composite MACE outcome measure (as described above) by race. The incidence rates were estimated based on time to the first event using Poisson distribution, with follow-up time censored at last contact. The Cox proportional hazards models described for the primary outcome above were expanded to include race and interaction of race and treatment, to evaluate modification of statin effect.
| events per 1000 person-years | Pitavastatin | Placebo |
|---|---|---|
| Among Asians | 1.6 (0.7 to 3.7) | 7.0 (4.6 to 10.6) |
| Among Blacks | 5.8 (4.3 to 7.7) | 8.7 (6.9 to 10.9) |
| Among Whites | 5.6 (4.1 to 7.7) | 7.5 (5.7 to 9.9) |
| Among Other | 5.0 (2.7 to 9.4) | 5.7 (3.1 to 10.6) |
Collected over From entry through end of study. Follow-up time varied depending on time of enrollment (the median follow-up time was 5.6 years).. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pitavastatin | 126/3,888 (3.2%) | 750/3,888 (19.3%) | 488/3,888 (12.6%) |
| Placebo | 143/3,881 (3.7%) | 755/3,881 (19.5%) | 420/3,881 (10.8%) |
| Event | Pitavastatin | Placebo |
|---|---|---|
| Lower respiratory tract and lung infectionsInfections and infestations | 71/3888 | 66/3881 |
| Limb fractures and dislocationsInjury, poisoning and procedural complications | 43/3888 | 50/3881 |
| Abdominal and gastrointestinal infectionsInfections and infestations | 36/3888 | 41/3881 |
| Bacterial infections NECInfections and infestations | 41/3888 | 30/3881 |
| Suicidal and self-injurious behaviourPsychiatric disorders | 33/3888 | 28/3881 |
| Bronchospasm and obstructionRespiratory, thoracic and mediastinal disorders | 30/3888 | 22/3881 |
| Renal failure and impairmentRenal and urinary disorders | 25/3888 | 24/3881 |
| Pain and discomfort NECGeneral disorders | 16/3888 | 24/3881 |
| Urinary tract infectionsInfections and infestations | 23/3888 | 15/3881 |
| Pulmonary thrombotic and embolic conditionsRespiratory, thoracic and mediastinal disorders | 11/3888 | 21/3881 |
| Event | Pitavastatin | Placebo |
|---|---|---|
| Diabetes mellitus (incl subtypes)Metabolism and nutrition disorders | 238/3888 | 184/3881 |
| Renal function analysesInvestigations | 125/3888 | 122/3881 |
| Muscle painsMusculoskeletal and connective tissue disorders | 77/3888 | 44/3881 |
| General nutritional disorders NECMetabolism and nutrition disorders | 66/3888 | 44/3881 |
| Physical examination procedures and organ system statusInvestigations | 62/3888 | 65/3881 |
| Vascular hypertensive disorders NECVascular disorders | 37/3888 | 50/3881 |
| Musculoskeletal and connective tissue pain and discomfortMusculoskeletal and connective tissue disorders | 40/3888 | 43/3881 |
All participants enrolled.
| Age, Continuous(years) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Median | 50 (45 to 55) | 50 (45 to 55) | 50 (45 to 55) |
| Age, Customized(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| 40-49 years | 1842 | 1888 | 3730 |
| 50-59 years | 1712 | 1649 | 3361 |
| ≥60 years | 334 | 344 | 678 |
| Sex/Gender, Customized(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Cisgender | 3691 | 3683 | 7374 |
| Transgender | 63 | 64 | 127 |
| Not reported | 134 | 134 | 268 |
| Sex: Female, Male(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Female | 1211 | 1208 | 2419 |
| Male | 2677 | 2673 | 5350 |
| Ethnicity (NIH/OMB)(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 366 | 332 | 698 |
| Not Hispanic or Latino | 1575 | 1611 | 3186 |
| Unknown or Not Reported | 16 | 18 | 34 |
| Race/Ethnicity, Customized(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Black | 1569 | 1639 | 3208 |
| White | 1364 | 1340 | 2704 |
| Asian | 571 | 567 | 1138 |
| Other | 384 | 335 | 719 |
| Region of Enrollment(participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| Haiti | 69 | 71 | 140 |
| United States | 1897 | 1890 | 3787 |
| Thailand | 304 | 286 | 590 |
| India | 246 | 258 | 504 |
| Spain | 106 | 107 | 213 |
| Canada | 60 | 71 | 131 |
| Botswana | 145 | 136 | 281 |
| Brazil | 546 | 553 | 1099 |
| South Africa | 282 | 288 | 570 |
| Uganda | 96 | 85 | 181 |
| Zimbabwe | 62 | 63 | 125 |
| Peru | 75 | 73 | 148 |
| Global burden of disease (GBD) region(Participants) | Pitavastatin | Placebo | Total |
|---|---|---|---|
| High income | 2044 | 2051 | 4095 |
| Latin America and Caribbean | 709 | 714 | 1423 |
| Southeast or East Asia | 304 | 286 | 590 |
| South Asia | 246 | 258 | 504 |
| Sub-Saharan Africa | 585 | 572 | 1157 |
8 further baseline measures are reported on the registry.
Showing the first 100 of 137 sites across 13 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2015 to primary completion in Aug 2023, 100 months.
Results were first posted in Oct 2024, 1 year 1 month after primary completion.
Of 40 non-industry phase 3 interventional studies under Cardiovascular Diseases, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 95. This study's 100 months is above that.
Counting every sponsor, half of 82 studies reached it within 57 months; a quarter within 34 and three quarters within 83.
Cardiovascular Diseases covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Pitavastatin
National Institute of Allergy and Infectious Diseases (NIAID) →