A Phase 3 interventional study of Empagliflozin and Placebo in Heart Failure, sponsored by Boehringer Ingelheim. Completed at 619 sites in 23 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-06-06.
Sponsored by Boehringer Ingelheim · Phase 3, Interventional, and Treatment
This is a study in adults with chronic heart failure. People with chronic heart failure may need to be hospitalised for their condition. Some people with chronic heart failure may eventually die from their condition. The purpose of the study is to find out whether a medicine called empagliflozin lowers the chances of patients having to go to hospital for heart failure and whether it improves their survival. The study is open to patients with a type of chronic heart failure called chronic heart failure with preserved ejection fraction.
Participants stay in the study until researchers have enough information about how effective empagliflozin is. It is expected that participants who enter at the very beginning of the enrolment period may be in the study for over 3 years, while participants who enter near the end of the enrolment period may be in the study for less than 2 years. The participants are put into 2 groups. It is decided by chance who gets into which group. One group gets empagliflozin tablets every day and the other group gets placebo tablets every day. Placebo tablets look like empagliflozin tablets but contain no medicine.
Participants visit the doctors regularly. During these visits, the doctors collect information about the participant's health. The doctors want to know how many patients had to go to hospital because of heart failure or who died from cardiovascular disease.
5,803 studies on the registry are indexed under Heart Failure; 1,222 are open to participants now.
This study's enrollment of 5,988 is above the median of 72 across 3,790 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Boehringer Ingelheim is the lead sponsor of 2,297 studies on the registry; 56 are open to participants now.
Of its 166 completed or terminated interventional studies of FDA-regulated products, 121 (73%) have results posted.
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Exclusion criteria:
Drug: Empagliflozin
Drug: Placebo
once daily
Also known as: JARDIANCE, JARDIANZ, GIBTULIO
once daily
Time to First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)
Failure with preserved Ejection Fraction (HFpEF). The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)
Reported is the total number of adjudicated HHF events (first and recurrent) which occurred.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
eGFR (CKD-EPI) cr Slope of Change From Baseline
Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR(CKD-EPI)cr) slope of change from baseline. Available on-treatment change-from-baseline data were used. The slope represents the long term effect of eGFR change from baseline and provides the yearly rate of decline. Timepoints after baseline were included in calculation of slope of change from baseline. The slope per patient was calculated using a random coefficient model with terms for treatment, region, baseline status of diabetes, age, sex, left ventricular ejection fraction (LVEF) and glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula (eGFR (CKD-EPI)cr) at baseline and in addition the factors "time", "treatment-by-time interaction", and "baseline eGFR (CKD-EPI)cr-by-time interaction".
Time frame: At baseline, week 4, 12, 32, 52, 76, 100, 124, 148, 172 and week 196, up to 1043 days.
Time to the First Event in the Composite Renal Endpoint: Chronic Dialysis, Renal Transplant, or Sustained Reduction in eGFR (CKD-EPI)cr
Chronic dialysis was defined as dialysis with a frequency of twice per week or more for at least 90 days. Sustained was determined by two or more consecutive post-baseline central laboratory measurement separated by at least 30 days. Reduction in glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) was defined as reduction in eGFR from baseline ≥40%, eGFR \<15 mL/min/1.73 m\^2 for patients with baseline eGFR ≥30 mL/min/1.73 m\^2, or eGFR \<10 mL/min/1.73 m\^2 for patients with baseline eGFR \<30 mL/min/1.73 m\^2. The incidence rate per 100 patient years (100 \* number of patients with event / time at risk \[years\]) is reported. Time at risk \[year\] is calculated as: Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Abbreviation: Patient-years (pt-yrs).
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
Time to First Adjudicated Hospitalisation for Heart Failure (HHF)
Time to first adjudicated HHF. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
Time to Adjudicated Cardiovascular (CV) Death
Time to adjudicated CV death. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
Time to All-cause Mortality
Time to all-cause mortality. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
Time to Onset of Diabetes Mellitus (DM) in Patients With Pre-DM
Time to onset of DM (defined as HbA1c ≥6.5% or as diagnosed by the investigator) in patients with pre-DM. Pre-DM was defined as no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of ≥5.7% and \<6.5%. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
Time frame: From randomization until completion of the planned treatment phase, to 1403 days.
Change From Baseline in Kansas City Cardiomyopathy Questionaire (KCCQ) Clinical Summary Score at Week 52
The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status. For patients who died, a worst score (score of 0) was imputed for the score at all subsequent scheduled visits after the date of death where the score would have been assessed. Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported.
Time frame: At baseline and at week 12, week 32 and week 52.
Occurrence of All-cause Hospitalisation (First and Recurrent)
Occurrence of all-cause hospitalisation (first and recurrent). Total number of all cause hospitalisations is reported.
Time frame: From randomization until completion of the planned treatment phase, up to 1403 days.
A randomised, double-blind trial to demonstrate superiority of empagliflozin versus placebo in patients with symptomatic, chronic heart failure and preserved left ventricular ejection fraction (LVEF\>40%) under stable treatment of heart failure symptoms.
| Milestone | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Started | 2991 | 2997 |
| Treated | 2989 | 2996 |
| Completed | 2046 | 2051 |
| Not completed | 945 | 946 |
| Withdrew: Adverse event | 553 | 575 |
| Withdrew: Protocol violation | 30 | 24 |
| Withdrew: Lost to follow-up | 6 | 16 |
| Withdrew: Patient refusal to continue, not due to ae | 304 | 284 |
| Withdrew: Study drug stopped, reason missing | 6 | 1 |
| Withdrew: Medical advice | 6 | 2 |
| Withdrew: Due to covid-19 pandemic | 2 | 8 |
| Withdrew: Investigator decision | 2 | 0 |
| Withdrew: Patient decision | 5 | 2 |
| Withdrew: Not attending study visits | 3 | 0 |
| Withdrew: Patient moved away | 3 | 4 |
| Withdrew: Other reason than stated above | 23 | 29 |
| Withdrew: Not treated | 2 | 1 |
Failure with preserved Ejection Fraction (HFpEF). The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
| Patients with event/100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF) | 8.67 (7.94 to 9.44) | 6.86 (6.22 to 7.54) |
Reported is the total number of adjudicated HHF events (first and recurrent) which occurred.
| HHF events | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent) | 541 | 407 |
Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR(CKD-EPI)cr) slope of change from baseline. Available on-treatment change-from-baseline data were used. The slope represents the long term effect of eGFR change from baseline and provides the yearly rate of decline. Timepoints after baseline were included in calculation of slope of change from baseline. The slope per patient was calculated using a random coefficient model with terms for treatment, region, baseline status of diabetes, age, sex, left ventricular ejection fraction (LVEF) and glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula (eGFR (CKD-EPI)cr) at baseline and in addition the factors "time", "treatment-by-time interaction", and "baseline eGFR (CKD-EPI)cr-by-time interaction".
| mL/min/ 1.73 meters squared/year | Placebo | 10 mg Empagliflozin |
|---|---|---|
| eGFR (CKD-EPI) cr Slope of Change From Baseline | -2.616 ± 0.108 | -1.253 ± 0.108 |
Chronic dialysis was defined as dialysis with a frequency of twice per week or more for at least 90 days. Sustained was determined by two or more consecutive post-baseline central laboratory measurement separated by at least 30 days. Reduction in glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) was defined as reduction in eGFR from baseline ≥40%, eGFR \<15 mL/min/1.73 m\^2 for patients with baseline eGFR ≥30 mL/min/1.73 m\^2, or eGFR \<10 mL/min/1.73 m\^2 for patients with baseline eGFR \<30 mL/min/1.73 m\^2. The incidence rate per 100 patient years (100 \* number of patients with event / time at risk \[years\]) is reported. Time at risk \[year\] is calculated as: Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Abbreviation: Patient-years (pt-yrs).
| Patients with event /100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to the First Event in the Composite Renal Endpoint: Chronic Dialysis, Renal Transplant, or Sustained Reduction in eGFR (CKD-EPI)cr | 2.23 (1.84 to 2.66) | 2.13 (1.74 to 2.54) |
Time to first adjudicated HHF. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
| Patients with event /100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to First Adjudicated Hospitalisation for Heart Failure (HHF) | 5.97 (5.37 to 6.62) | 4.28 (3.78 to 4.82) |
Time to adjudicated CV death. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
| Patients with event /100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to Adjudicated Cardiovascular (CV) Death | 3.81 (3.35 to 4.31) | 3.42 (2.98 to 3.89) |
Time to all-cause mortality. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
| Patients with event /100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to All-cause Mortality | 6.67 (6.05 to 7.32) | 6.60 (5.98 to 7.24) |
Time to onset of DM (defined as HbA1c ≥6.5% or as diagnosed by the investigator) in patients with pre-DM. Pre-DM was defined as no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of ≥5.7% and \<6.5%. The incidence rate per 100 patient years (pt-yrs) is presented and calculated as followed: Incidence rate per 100 pt-yrs = 100 \* number of patients with event / time at risk \[years\]. Time at risk \[years\] = Sum of time at risk \[days\] over all patients in a treatment group / 365.25. Patients without a specific endpoint event were censored at the last date the patient was known to be free of the event or at the end of the planned treatment period, whichever was earlier.
| Patients with event /100 pt-yrs at risk | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Time to Onset of Diabetes Mellitus (DM) in Patients With Pre-DM | 7.39 (6.21 to 8.68) | 6.12 (5.07 to 7.26) |
The KCCQ is a 23-item self-administered questionnaire designed to evaluate physical limitations, symptoms (frequency, severity, and changes over time), social limitations, self-efficacy, and quality of life in patients with Heart Failure. The KCCQ-clinical summary score comprises the following domains: Symptom frequency, symptom burden and physical limitation. The score is calculated by summing domain responses and then transforming scores to a 0-100 unit scale with higher scores indicating better health status. For patients who died, a worst score (score of 0) was imputed for the score at all subsequent scheduled visits after the date of death where the score would have been assessed. Change from baseline in KCCQ-score at week 52 was modeled using a MMRM with visit (week 12, 32 and 52) as repeated measures, adjusted mean (standard error) at week 52 is reported.
| Score on a scale | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Change From Baseline in Kansas City Cardiomyopathy Questionaire (KCCQ) Clinical Summary Score at Week 52 | 3.18 ± 0.31 | 4.51 ± 0.31 |
Occurrence of all-cause hospitalisation (first and recurrent). Total number of all cause hospitalisations is reported.
| Events of all-cause hospitialisations | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Occurrence of All-cause Hospitalisation (First and Recurrent) | 2769 | 2566 |
Collected over [All-cause Mortality]: From study start until end of study, up to 1438 days. [Serious adverse events (AE) and other AE]:From time of the first drug intake until 7 days (Residual Effect Period) after the last drug intake, up to 1410 days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 427/2,991 (14.3%) | 1,543/2,989 (51.6%) | 1,274/2,989 (42.6%) |
| 10 mg Empagliflozin | 422/2,997 (14.1%) | 1,436/2,996 (47.9%) | 1,191/2,996 (39.8%) |
| Event | Placebo | 10 mg Empagliflozin |
|---|---|---|
| Cardiac failureCardiac disorders | 594/2989 | 448/2996 |
| PneumoniaInfections and infestations | 119/2989 | 100/2996 |
| Acute kidney injuryRenal and urinary disorders | 107/2989 | 81/2996 |
| Atrial fibrillationCardiac disorders | 80/2989 | 92/2996 |
| Cardiac failure congestiveCardiac disorders | 66/2989 | 57/2996 |
| DeathGeneral disorders | 38/2989 | 56/2996 |
| Acute myocardial infarctionCardiac disorders | 48/2989 | 50/2996 |
| COVID-19Infections and infestations | 47/2989 | 49/2996 |
| Renal impairmentRenal and urinary disorders | 42/2989 | 38/2996 |
| Ischaemic strokeNervous system disorders | 35/2989 | 42/2996 |
| Event | Placebo | 10 mg Empagliflozin |
|---|---|---|
| HypertensionVascular disorders | 248/2989 | 212/2996 |
| HypotensionVascular disorders | 176/2989 | 212/2996 |
| HyperuricaemiaMetabolism and nutrition disorders | 208/2989 | 131/2996 |
| Urinary tract infectionInfections and infestations | 160/2989 | 207/2996 |
| Diabetes mellitusMetabolism and nutrition disorders | 200/2989 | 139/2996 |
| HyperkalaemiaMetabolism and nutrition disorders | 194/2989 | 170/2996 |
| FallInjury, poisoning and procedural complications | 193/2989 | 189/2996 |
| Renal impairmentRenal and urinary disorders | 181/2989 | 177/2996 |
| AnaemiaBlood and lymphatic system disorders | 164/2989 | 119/2996 |
| Atrial fibrillationCardiac disorders | 156/2989 | 137/2996 |
Randomised Set (RS), including all randomised patients.
| Age, Continuous(Years) | Placebo | 10 mg Empagliflozin | Total |
|---|---|---|---|
| Mean | 71.9 ± 9.6 | 71.8 ± 9.3 | 71.9 ± 9.4 |
| Sex: Female, Male(Participants) | Placebo | 10 mg Empagliflozin | Total |
|---|---|---|---|
| Female | 1338 | 1338 | 2676 |
| Male | 1653 | 1659 | 3312 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | 10 mg Empagliflozin | Total |
|---|---|---|---|
| Hispanic or Latino | 754 | 770 | 1524 |
| Not Hispanic or Latino | 2236 | 2227 | 4463 |
| Unknown or Not Reported | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | Placebo | 10 mg Empagliflozin | Total |
|---|---|---|---|
| American Indian or Alaska Native | 104 | 90 | 194 |
| Asian | 411 | 413 | 824 |
| Native Hawaiian or Other Pacific Islander | 19 | 14 | 33 |
| Black or African American | 125 | 133 | 258 |
| White | 2256 | 2286 | 4542 |
| More than one race | 75 | 60 | 135 |
| Unknown or Not Reported | 1 | 1 | 2 |
Showing the first 100 of 619 sites across 23 countries.
Documents are hosted by the registry — open the source record to download them.
Ran from Mar 2017 to primary completion in Apr 2021, 49 months.
Results were first posted in Jun 2022, 1 year 1 month after primary completion.
Of 65 industry-sponsored phase 3 interventional studies under Heart Failure, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 44. This study's 49 months is above that.
Counting every sponsor, half of 143 studies reached it within 39 months; a quarter within 25 and three quarters within 57.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Empagliflozin