A Phase III Randomised, Double-blind Trial to Evaluate the Effect of 12 Weeks Treatment of Once Daily EMPagliflozin 10 mg Compared With Placebo on ExeRcise Ability and Heart Failure Symptoms, In Patients With Chronic HeArt FaiLure With Reduced Ejection Fraction (HFrEF) (EMPERIAL-reduced)

Boehringer Ingelheim108 sites in 4 countries312 target enrollmentMarch 20, 2018

ConditionsHeart Failure

InterventionsEmpagliflozin Placebo

DrugsEmpagliflozin Placebo

Overview

Phase: Phase 3
Intervention: Empagliflozin
Conditions: Heart Failure
Sponsor: Boehringer Ingelheim
Enrollment: 312
Locations: 108
Primary Endpoint: Change From Baseline to Week 12 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary objective of the study is to evaluate the effect of empagliflozin 10 mg versus placebo on exercise ability using the 6 minute walk test in patients with chronic HF with reduced ejection fraction (LVEF ≤ 40%) Secondary objectives are to assess Patient-Reported Outcome (PRO)

Registry

clinicaltrials.gov

Start Date

March 20, 2018

End Date

October 7, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Of full age of consent (according to local legislation, usually ≥ 18 years) at screening.
•Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
•Signed and dated written informed consent in accordance with ICHGCP and local legislation prior to admission to the trial
•6MWT distance ≤350 m at screening and at baseline.
•Patients with chronic HF diagnosed for at least 3 months before Visit 1 and currently in NYHA class II-IV
•Chronic HF with reduced EF defined as LVEF ≤ 40 % as per echocardiography at Visit 1 as per local reading (obtained under stable condition).
•Elevated NT-proBNP \> 450 pg/ml for patients without atrial fibrillation (AF) OR NTproBNP \> 600 pg/ml for patients with AF as analysed at the Central laboratory at Visit 1
•Patients must be clinically stable and on appropriate and stable dose of medical therapy for HF (such as ACEi, ARB, β-blocker, oral diuretics, MRA, ARNI, ivabradine), consistent with prevailing CV guidelines, stable for at least 4 weeks prior to Visit 1(screening) with the exception of diuretics which must have been stable for at least two weeks prior to Visit
•The investigator must document the reason in case the patient is not on such medication or if not on target dose of any heart failure medication as per local guidelines.
•Clinically stable at randomization with no signs of heart failure decompensation (as per investigator judgement).

Exclusion Criteria

•Myocardial infarction (increase in cardiac enzymes in combination with symptoms of ischaemia or newly developed ischaemic ECG changes), coronary artery bypass graft surgery or other major cardiovascular surgery, stroke or TIA in past 90 days prior to Visit 1
•Acute decompensated HF (exacerbation of chronic HF) requiring intravenous (i.v.) diuretics, i.v. inotropes or i.v. vasodilators, or left ventricular assist device within 4 weeks prior to Visit 1, and/or during screening period until Visit 2
•Previous or current randomisation in another Empagliflozin Heart Failure trial (i.e. studies 1245.110, 1245.121, 1245-0167)
•Type 1 Diabetes Mellitus (T1DM)
•Impaired renal function, defined as eGFR \< 20 mL/min/1.73 m2 (CKD-EPIcr) or requiring dialysis, as determined at Visit 1
•Symptomatic hypotension or a SBP \< 100 mmHg at Visit 1 or 2
•Systolic blood pressure (SBP) ≥ 180 mmHg at Visit 1 or 2, or SBP \>160mmHg at both Visit 1 and 2
•Atrial fibrillation or atrial flutter with a resting heart rate \>110 bpm documented by ECG at Visit 1 (Screening)
•Unstable angina pectoris in past 30 days prior to Visit 1
•Largest distance walked in 6 minutes (6MWTD) at baseline \<100m.

Arms & Interventions

Empagliflozin

Intervention: Empagliflozin

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Change From Baseline to Week 12 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance

Time Frame: At baseline and at week 12

Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. If repeated 6MWT measurements were available for the same day, the longest distance was used for analysis. Change from baseline was defined as the distance walked in 6 minutes at week 12 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication. If a participant was present at the visit at week 12 but did not perform the 6MWT, the participant was evaluated as having walked a distance of 0 meter. If no value was available for week 12, an imputed value was used. Patients with missing week 12 data who had no clinical event were ranked below any patient with non-missing data, but above the patients who had clinical events. Patients who died before week 12 were ranked below the patients in all categories above.

Secondary Outcomes

Relative Change From Baseline to Week 12 in N-terminal Pro-brain Natriuretic Peptide (NTproBNP)(Within 3 weeks prior to treatment start and at Week 12)
Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)(At baseline and at week 12)
Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms(At baseline and at week 12)
Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12(At week 12)
Change From Baseline to Week 6 in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance(At baseline and at week 6)
Change From Baseline to Week 12 in Clinical Congestion Score(At baseline and at week 12)
Change From Baseline to Week 12 in Chronic Heart Failure Questionnaire Self- Administered Standardized Format (CHQ-SAS) Dyspnea Score(At baseline and at week 12)
Change From Baseline to Week 12 in Patient Global Impression of Severity (PGI-S) of Dyspnoea(At baseline and at week 12)
Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12(At week 12)