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 Preserved Ejection Fraction (HFpEF) (EMPERIAL - Preserved)
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Heart Failure
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 315
- Locations
- 107
- Primary Endpoint
- Change From Baseline to Week 12 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes in Standardised Conditions (6MWTD)
- Status
- Completed
- Last Updated
- 5 years ago
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 (6MWT) in patients with chronic heart failure (CHF) with preserved ejection fraction (LVEF > 40%).
Secondary objectives are to assess Patient-Reported Outcome (PRO)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Of full age of consent (according to local legislation, usually ≥ 18 years) at screening.
- •Male or female patients. Women of child bearing potential (WOCBP) 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
- •Six minute walk test (6MWT) distance ≤350 m at screening and at baseline.
- •Patients with CHF diagnosed for at least 3 months before Visit 1, and currently in NYHA class II-IV
- •Chronic heart failure (CHF) with preserved Ejection fraction (EF) defined as left ventricle ejection fraction(LVEF) \> 40 % as per echocardiography at Visit 1 per local reading and no prior measurement of LVEF ≤ 40% under stable conditions.
- •Elevated N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) \> 300 pg/ml for patients without atrial fibrillation (AF), OR \> 600 pg/ml for patients with AF, as analysed at the Central laboratory at Visit 1
- •Patients must have at least one of the following evidence of heart failure (HF):
- •Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) documented by echocardiogram at Visit 1, OR
- •Documented Hospitalization for Heart Failure (HHF) within 12 months prior to Visit 1
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 transient ischemic attack in past 90 days prior to Visit 1
- •Acute decompensated HF (exacerbation of CHF) 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, 1245-0168)
- •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 systolic blood pressure (SBP) \< 100 mmHg at Visit 1 or 2
- •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
Placebo
Intervention: Placebo
Empagliflozin
Intervention: Empagliflozin
Outcomes
Primary Outcomes
Change From Baseline to Week 12 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes in Standardised Conditions (6MWTD)
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 (6MWTD). If repeated 6-minutes walk test (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
- Change From Baseline in Patient Global Impression of Severity (PGI-S) of Dyspnea Severity at Week 12(At baseline 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)
- Relative Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NTproBNP) at Week 12(Within 3 weeks prior to treatment start and at Week 12.)
- Change From Baseline to Week 6 in Exercise Capacity as Measured by the Distance Walked in 6 Minutes(At baseline and at Week 6)
- 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 in Clinical Congestion Score at Week 12(At baseline and at Week 12)
- Patient Global Impression of Change (PGI-C) in Dyspnea at Week 12(Week 12)
- Change From Baseline in Patient Global Impression of Severity (PGI-S) of Heart Failure Symptoms at Week 12(At baseline and at Week 12)
- Patient Global Impression of Change (PGI-C) in Heart Failure Symptoms at Week 12(Week 12)