A Phase 4 interventional study of efavirenz and nucleoside in Cryptococcal Meningitis, HIV Infections and AIDS, sponsored by University of Minnesota. Completed at 3 sites in 2 countries. Open to participants aged 14 Years and older. Per ClinicalTrials.gov, last updated 2020-06-09.
Sponsored by University of Minnesota · Phase 4, Interventional, and Treatment
The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient.
After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:
HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.
54 studies on the registry are indexed under Meningitis, Cryptococcal; 6 are open to participants now.
This study's enrollment of 177 is above the median of 143 across 35 interventional studies indexed under Meningitis, Cryptococcal.
Browse Meningitis, Cryptococcal studies →University of Minnesota is the lead sponsor of 1,216 studies on the registry; 197 are open to participants now.
Of its 136 completed or terminated interventional studies of FDA-regulated products, 95 (70%) 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.
Exclusion Criteria:
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.
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 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 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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
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.
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.
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.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
Drug: efavirenz · Biological: nucleoside
HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week). HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
Drug: efavirenz · Biological: nucleoside
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.
Also known as: sustiva
Treatment strategy of when to initiate first line HIV therapy after cryptococcal meningitis diagnosis.
Also known as: zidovudine or stavudine, lamivudine
Mortality
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
Time frame: 26 weeks from study entry
Incidence of Immune Reconstitution Inflammatory Syndrome
Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
Time frame: 46 weeks
Incidence of Cryptococcal-relapse
Incidence of culture positive cryptococcal meningitis relapse
Time frame: 46 weeks
Safety of ART Initiation
Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.
Time frame: 46 weeks
46-week Survival
46-week survival by time-to-event analysis of all subjects enrolled
Time frame: 46 weeks
HIV-1 Viral Suppression
HIV-1 virologic suppression to \<400 copies/mL at 26-weeks after enrollment
Time frame: 26 weeks
Antiretroviral Therapy Tolerability
Incidence of antiretroviral therapy interruption by \>=3 consecutive days
Time frame: 26 weeks
Karnofsky Functional Status
Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
Time frame: 46 weeks
Microbiologic Clearance
Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.
Time frame: 4 weeks
Percentage of Participants, Per CSF WBC Subgroup, Who Died by Week 26
Percentage of Participants who died by week 26 based on CSF white blood cell (WBC) count at study entry (time of randomization at a median of 8 days of anti-fungal therapy).
Time frame: 26 weeks
| Milestone | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Started | 88 | 89 |
| Completed | 87 | 89 |
| Not completed | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 |
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Mortality | 40 | 27 |
Incidence of cryptococcal-related immune reconstitution inflammatory syndrome through 46 weeks after enrollment.
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Incidence of Immune Reconstitution Inflammatory Syndrome | 17 | 9 |
Incidence of culture positive cryptococcal meningitis relapse
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Incidence of Cryptococcal-relapse | 2 | 8 |
Incidence of Adverse Events (Grade 3,4,5) through 46-weeks, as defined by the National Institute of Allergy and Infectious Diseases, Division of AIDS toxicity classification scale, version 2009.
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Safety of ART Initiation | 73 | 75 |
46-week survival by time-to-event analysis of all subjects enrolled
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| 46-week Survival | 41 | 29 |
HIV-1 virologic suppression to \<400 copies/mL at 26-weeks after enrollment
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| HIV-1 Viral Suppression | 43 | 49 |
Incidence of antiretroviral therapy interruption by \>=3 consecutive days
| participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Antiretroviral Therapy Tolerability | 5 | 1 |
Functional status via Karnofsky performance status score at 4, 26, 46 weeks. Karnofsky Scale: 100 - Normal; no complaints; no evidence of disease. 90 - Able to carry on normal activity; minor signs or symptoms of disease. 80 - Normal activity with effort; some signs or symptoms of disease. 70 - Cares for self; unable to carry on normal activity or to do active work. 60 - Requires occasional assistance, but is able to care for most of his personal needs. 50 - Requires considerable assistance and frequent medical care. 40 - Disabled; requires special care and assistance. 30 - Severely disabled; hospital admission is indicated although death not imminent. 20 - Very sick; hospital admission necessary; active supportive treatment necessary. 10 - Moribund; fatal processes progressing rapidly. 0 - Dead
| Scores on a scale | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| 4 weeks | 70 ± 19 | 70 ± 19 |
| 26 weeks | 93 ± 7 | 93 ± 10 |
| 46 weeks | 92 ± 10 | 95 ± 8 |
Microbiologic clearance of cryptococcus as measured by serial quantitative cryptococcal cultures collected at diagnosis through 14 days of amphotericin therapy. The early fungicidal activity (EFA) of the rate of clearance is expressed as log10 colony forming units (CFU) of Cryptococcus neoformans per mL of CSF per day.
| log10 CFU/mL/day | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| EFA by mixed effects model | -0.31 (-0.34 to -0.28) | -0.31 (-0.34 to -0.28) |
| EFA by linear regression | -0.39 (-0.45 to -0.32) | -0.35 (-0.39 to -0.31) |
Percentage of Participants who died by week 26 based on CSF white blood cell (WBC) count at study entry (time of randomization at a median of 8 days of anti-fungal therapy).
| percentage of participants | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| CSF WBC <5 /mcl (n=33, 31) | 48.5 | 16.1 |
| CSF WBC >5/mcL (n=42, 40) | 40.5 | 45 |
Collected over 46 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Earlier HIV Therapy | — | 49/88 (55.7%) | 73/88 (83%) |
| Deferred HIV Therapy | — | 53/89 (59.6%) | 75/89 (84.3%) |
| Event | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| Grade 4 Serious AEsNervous system disorders | 38/88 | 42/89 |
| Grade 3 Serious AEsNervous system disorders | 40/88 | 38/89 |
| Grade 5 AEsNervous system disorders | 11/88 | 5/89 |
| Event | Earlier HIV Therapy | Deferred HIV Therapy |
|---|---|---|
| HematologyBlood and lymphatic system disorders | 41/88 | 47/89 |
| ChemistriesMetabolism and nutrition disorders | 32/88 | 25/89 |
| InfectionInfections and infestations | 10/88 | 18/89 |
HIV-infected persons not previously receiving HIV therapy with first episode of cryptococcal meningitis diagnosed by CSF culture and/or CSF cryptococcal antigen testing.
| Age, Continuous(years) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Median | 35 (28 to 40) | 36 (30 to 40) | 35 (29 to 40) |
| Sex: Female, Male(Participants) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Female | 42 | 42 | 84 |
| Male | 46 | 47 | 93 |
| Race (NIH/OMB)(Participants) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 88 | 89 | 177 |
| White | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Uganda | 75 | 77 | 152 |
| South Africa | 13 | 12 | 25 |
| CD4 Count, baseline(cells/mcL) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Median | 19 (9 to 69) | 28 (11 to 76) | 23 (10 to 73) |
| CSF Quantitative Culture, baseline(log10 colony forming units/mL of CSF) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Median | 5.3 (4.2 to 5.7) | 4.8 (3.8 to 5.5) | 5.1 (4.0 to 5.6) |
| CSF Cryptococcal Antigen titer, 1:xxxx(titers) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Median | 8000 (2000 to 16000) | 4000 (1000 to 14400) | 6400 (2000 to 16000) |
| HIV-1 Viral Load(log10 copies/mL) | Earlier HIV Therapy | Deferred HIV Therapy | Total |
|---|---|---|---|
| Median | 5.5 (5.2 to 5.8) | 5.5 (5.3 to 5.8) | 5.5 (5.2 to 5.8) |
This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Efavirenz · Nucleosides