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 antagonis

- 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