DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction
Condition: Heart Failure With Reduced Ejection Fraction (HFrEF)
MeSH terms: Heart Failure
Intervention: Dapagliflozin; Placebo
Intervention description: Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.; Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 313.0
Sex: All
Minimum age: 18 Years
Maximum age: 150 Years
Healthy volunteers: No

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)
    

Eligibility 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