Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure
Condition: Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
MeSH terms: Heart Failure
Intervention: Dapagliflozin; Placebo
Intervention description: 10 mg or 5 mg tablets given once daily, per oral use.; Placebo matching dapagliflozin 10 mg or 5 mg.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4744.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: HFrEF; Heart Failure (HF); Cardiovascular Events (CV); Phase III outcome trial

Summary:

      The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of
      worsening heart failure or cardiovascular death in patients with chronic heart failure with
      reduced ejection fraction
    

Eligibility criteria:

        Inclusion Criteria:

          -  Provision of signed informed consent prior to any study specific procedures

          -  Male or female, aged ≥18 years

          -  Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV),
             which has been present for at least 2 months

          -  LVEF≤40%

          -  Elevated NT-proBNP levels

          -  Patients should receive background standard of care for HFrEF and be treated according
             to locally recognized guidelines

          -  eGFR ≥30 mL/min/1.73 m^2 (CKD-EPI formula) at enrolment (visit 1)

        Exclusion Criteria:

          -  Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or
             previous intolerance of an SGLT2 inhibitor

          -  Type 1 diabetes mellitus

          -  Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements either at
             visit 1 or visit 2

          -  Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks
             prior to enrolment

          -  MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to
             enrolment

          -  Coronary revascularization (percutaneous coronary intervention or coronary artery
             bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or
             planned to undergo any of these operations after randomization

          -  Implantation of a CRT within 12 weeks prior to enrolment or intent to implant a CRT
             device

          -  Previous cardiac transplantation or implantation of a ventricular assistance device or
             similar device, or implantation expected after randomization

          -  HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis,
             hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease

          -  Symptomatic bradycardia or second or third degree heart block without a pacemaker

          -  Severe (eGFR <30 mL/min/1.73 m^2 by CKD-EPI), unstable or rapidly progressing renal
             disease at the time of randomization