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

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