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Completed

NCT Number: NCT03057977

EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced)

The aim of the study is to investigate the safety and efficacy of empagliflozin versus placebo on top of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction.

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Key information

Conditions

Heart Failure Cardiovascular Diseases Heart Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital Interzonal General de Agudos Dr Jose Penna, Bahía Blanca, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female patient age >= 18 years at screening. For Japan only: Age >= 20 years at screening
  • Patients with chronic HF (Chronic Heart Failure) NYHA (New York Heart Association Classification) class II-IV and reduced EF (Ejection Fraction) (LVEF (Left Ventricular Ejection Fraction) <=40%) and elevated NT-proBNP (N-terminal of the prohormone brain natriuretic peptide)
  • If EF >= 36% to <= 40%: NT-proBNP >= 2500 pg/ml or patients without AF (atrial fibrillation/atrial flutter) and NT-proBNP >= 5000 pg/ml for patients with AF
  • If EF >= 31% to <= 35%: NT-proBNP >= 1000 pg/ml for patients without AF and NT-proBNP >=2000 pg/ml for patients with AF
  • If EF<= 30%: NT-proBNP >= 600 pg/ml for patients without AF and NT-proBNP >=1200 pg/ml for patients with AF
  • EF ≤ 40% and hospitalization for heart failure in the past 12 months: NTproBNP ≥ 600 pg/ml for patients without AF and NT-proBNP >= 1200 pg/ml for patients with AF
  • Appropriate dose of medical therapy for HF consistent with prevailing local and international CV (Cardiovascular) guidelines, stable for at least 1 week prior to Visit 1
  • Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines
  • Signed and dated written ICF (Informed Consent Form)
  • Further inclusion criteria apply

Exclusion criteria

  • Myocardial infarction, coronary artery bypass graft surgery, or other major cardiovascular surgery, stroke or TIA (Transient Ischaemic Attack) in past 90 days prior to Visit 1
  • Heart transplant recipient, or listed for heart transplant
  • Acute decompensated HF
  • Systolic blood pressure (SBP) >= 180 mmHg at Visit 2.
  • Symptomatic hypotension and/or a SBP < 100 mmHg
  • Indication of liver disease
  • Impaired renal function, defined as eGFR (Estimated Glomerular Filtration Rate) < 20 mL/min/1.73 m2 (CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration Equation)) or requiring dialysis
  • History of ketoacidosis
  • Current use or prior use of a SGLT (Sodium-glucose co-transporter)-2 inhibitor or combined SGLT-1 and 2 inhibitor
  • Currently enrolled in another investigational device or drug study
  • Known allergy or hypersensitivity to empagliflozin or other SGLT-2 inhibitors
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Further exclusion criteria apply

Treatment and study plan

Empagliflozin

Drug

once daily

Other names: JARDIANCE, JARDIANZ, GIBTULIO

Placebo

Drug

once daily

Primary outcomes

  1. Time to the First Event of Adjudicated Cardiovascular (CV) Death or Adjudicated Hospitalisation for Heart Failure (HHF)

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to the first event of adjudicated cardiovascular (CV) death or adjudicated hospitalisation for heart failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

Secondary outcomes

  1. Occurrence of Adjudicated Hospitalisation for Heart Failure (HHF) (First and Recurrent)

    Time frame: From randomisation until completion of the planned treatment phase, up to 1040 days.

    Reported is the total number of HHF events (first and recurrent) which occurred.

    All data up to the end of the planned treatment period (including the data after the end of treatment for patients not completing the treatment period as planned) from all randomised patients was used.

  2. eGFR (CKD-EPI) cr Slope of Change From Baseline

    Time frame: Assessed at baseline, week 4, 12, 32, 52, 76, 100, 124, 148 and at end of treatment (EOT), up to 1040 days.

    Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr) [mL/min/1.73m2] slope of change from baseline.

    Available on-treatment change-from-baseline data were to be used. Patients without on-treatment data after randomisation were not to be included in this analysis. Slope represents the long term effect on eGFR.

    Timepoints after baseline were included in calculation of slope of change from baseline. Descriptive statistic (mean(standard error)) is reported.

  3. Time to First Event in Composite Renal Endpoint: Chronic Dialysis, Renal Transplant or Sustained Reduction of eGFR(CKD-EPI)cr

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to the first event in the composite renal endpoint: chronic dialysis (with a frequency of twice per week or more for at least 90 days), renal transplant, or sustained reduction in Glomerular filtration rate estimated by the chronic kidney disease epidemiology collaboration formula with serum creatinine measurement (eGFR (CKD-EPI)cr).

    The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

  4. Time to First Adjudicated Hospitalisation for Heart Failure (HHF)

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to first adjudicated Hospitalisation for Heart Failure (HHF). The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

  5. Time to Adjudicated Cardiovascular (CV) Death

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to adjudicated CV (Cardiovascular) death. The incidence rate (patients with events per 100 person years at risk) is reported.

    The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

  6. Time to All-cause Mortality

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to all-cause mortality. The incidence rate (patients with events per 100 person years at risk) is reported.

    The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

  7. Time to Onset of Diabetes Mellitus (DM)

    Time frame: From randomisation until completion of the planned treatment period, up to 1040 days.

    Time to onset of DM (Glycated haemoglobin (HbA1c) ≥6.5% or as diagnosed by the investigator) in patients with pre-DM (no history of DM and no HbA1c ≥6.5% before treatment, and a pre-treatment HbA1c value of 5.7 to <6.5%). The incidence rate (patients with events per 100 person years at risk) is reported.

    The incidence rate per 100 patient years (100 * number of patients with event /time at risk [years]) is presented. With time at risk [year] calculated as: 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.

    Unit of Measure: Patients with events per 100 patient-years (pt-yrs) at risk.

  8. Change From Baseline in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score at Week 52

    Time frame: Assessed at baseline, week 12, week 32 and week 52.

    Change from baseline in KCCQ (Kansas City cardiomyopathy questionnaire) 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, selfefficacy, 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) is imputed at all subsequent scheduled visits after the date of death.

    Standard error is adjusted standard error. 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.

  9. Number of All-cause Hospitalizations (First and Recurrent)

    Time frame: From randomisation until completion of the planned treatment phase, up to 1040 days.

    Number of all-cause hospitalizations (first and recurrent).

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Collaborators

  • Eli Lilly and Company

Registry information

Official study title

A Phase III Randomised, Double-blind Trial to Evaluate Efficacy and Safety of Once Daily Empagliflozin 10 mg Compared to Placebo, in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Feb 20, 2017
Registry last updated
May 18, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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