DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction

• Status: Completed
• Trial end date: 2020-03-07
• Target enrollment: 0
• Participant gender: All

Summary

International, Multicentre, Parallel-group, Randomised, Double-blind, Placebo-controlled, Phase III Study Evaluating the effect of Dapagliflozin on Exercise Capacity in Heart Failure Patients with Reduced Ejection Fraction (HFrEF)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AstraZeneca
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin

Criteria

Inclusion Criteria:

• Provision of signed informed consent prior to any study specific procedures

• Male or female, aged ≥18 years

• Documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 8 weeks

• LVEF≤40%

• Elevated NT-proBNP levels

• Patients should receive background standard of care as described below: All HFrEF patients should be treated according to locally recognised guidelines on standard of care treatment with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimised and stable for ≥4 weeks (this does not apply to diuretics) before visit 1 and include (unless contraindicated or not tolerated):

• an ACE inhibitor, or ARB or sacubitril/valsartan and

• a beta-blocker and

• if considered appropriate by the patient's treating physician; a mineral corticoid receptor antagonist

• 6MWD≥100 metres and ≤425 metres at enrolment and randomization.

Exclusion Criteria:

• Presence of any condition that precludes exercise testing

• Participation in a structured exercise training programme in the 1 month prior to screening or planned to start during the trial

• Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor

• Type 1 diabetes mellitus

• eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at enrolment, unstable or rapidly progressing renal disease at time of randomisation

• Systolic BP <95 mmHg on 2 consecutive measurements

• Systolic BP ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements

• Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment

• MI, unstable angina, coronary revascularization ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronization therapy device within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization.

• Stroke or transient ischemic attack within 12 weeks prior to enrolment.

• Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.

• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization

• HF due to infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease