This Study Tests Empagliflozin in Patients With Chronic Heart Failure With Reduced Ejection Fraction (HFrEF). The Study Looks at How Far Patients Can Walk in 6 Minutes and at Their Heart Failure Symptoms

Boehringer Ingelheim312 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

312

Conditions

Heart Failure

Interventions

EmpagliflozinDRUG

Film-coated tablet

PlaceboDRUG

Film-coated tablet

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 1. 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). * Appropriate use of medical devices such as cardioverter defibrillator (ICD) or a cardiac resynchronization therapy (CRT) consistent with prevailing local or international CV guidelines, and if a device is required, it must have been implanted for at least 3 months prior to visit 1 for CRT and 1 month prior to visit 1 for ICD. 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. * Any presence of condition that precludes exercise testing such as: * claudication, * uncontrolled (according to investigator judgement) bradyarrhythmia or tachyarrhythmia, * significant musculoskeletal disease, * primary pulmonary hypertension, * severe obesity (body mass index ≥40.0 kg/m2), * orthopedic conditions that limit the ability to walk (such as arthritis in the leg, knee or hip injuries) * amputation with artificial limb without stable prosthesis function for the past 3 months * Any condition that, in the opinion of the investigator, would contraindicate the assessment of 6MWT * Patients in a structured (according to Investigator judgement) exercise training program in the 1 month prior to screening or planned to start one during the course of this trial. * Planned implantation of ICD or CRT during the course of the trial. * Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening * Treatment with i.v. iron therapy or erythropoietin within 3 months prior to screening * Further exclusion criteria applies

Locations (109)

Outcomes

Primary Outcomes

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

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.

Time frame: At baseline and at week 12

Secondary Outcomes

Change From Baseline to Week 12 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score (TSS)

Change from baseline in KCCQ-TSS was defined as the endpoint value at week 12 minus the last available measurement before start of treatment with randomised study medication. The KCCQ is 23 item self-administered questionnaire and comprises 7 domains: physical limitation, symptom frequency, symptom burden, symptom stability, social limitation, self-efficacy and quality of life. Additionally 3 summary scores exist: TSS, clinical summary score, and overall summary score. The scores of the KCCQ domains and summary scores range from 0 to 100, with higher score indicating better outcome. If no questionnaire was available at 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. If no questionnaire was available at baseline, change from baseline was not imputed.

Time frame: 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

Data from ClinicalTrials.gov

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