Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure.
Condition: Heart Failure With Preserved Ejection Fraction
MeSH terms: Heart Failure
Intervention: Dapagliflozin; Placebo
Intervention description: 10 mg tablets given once daily, per oral use.; Placebo matching dapagliflozin 10 mg
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: International, Double-blind, Randomised, Placebo-Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 6263.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No

Summary:

      This is an international, multicentre, parallel-group, event-driven, randomised,
      double-blind, placebo-controlled study in HFpEF patients, evaluating the effect of
      dapagliflozin 10 mg versus placebo, given once daily in addition to background regional
      standard of care therapy, including treatments to control co-morbidities, in reducing the
      composite of CV death or heart failure events.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provision of signed informed consent prior to any study specific procedures.

          2. Male or female patients age ≥40 years.

          3. Documented diagnosis of symptomatic heart failure (NYHA class II-IV) at enrolment, and
             a medical history of typical symptoms/signs of heart failure ≥6 weeks before enrolment
             with at least intermittent need for diuretic treatment.

          4. Left Ventricular Ejection Fraction (LVEF) >40% and evidence of structural heart
             disease (i.e. left ventricular hypertrophy or left atrial enlargement ) documented by
             the most recent echocardiogram, and/or cardiac MR within the last 12 months prior to
             enrolment. For patients with prior acute cardiac events or procedures that may reduce
             LVEF, e.g. as defined in exclusion criterion 6, qualifying cardiac imaging assessment
             at least 12 weeks following the procedure/event is required.

          5. Elevated NT-pro BNP levels.

          6. Both ambulatory and hospitalised patients may be enrolled and randomised. Patients
             currently hospitalised for HF, must be off intravenous HF medications for at least 24
             before randomisation.

        Further details regarding inclusion criteria 4-6 may apply.

        Exclusion Criteria:

          1. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or
             previous intolerance to an SGLT2 inhibitor.

          2. Type 1 diabetes mellitus (T1D).

          3. eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at Visit 1.

          4. Systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements at 5-minute
             intervals, at Visit 1 or at Visit 2.

          5. Systolic BP≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications
             or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at 5-minute
             intervals, at Visit 1 or at Visit 2.

          6. MI, unstable angina, coronary revascularization (percutaneous coronary intervention
             (PCI) or coronary artery bypass grafting (CABG)), ablation of atrial
             flutter/fibrillation, valve repair/replacement within 12 weeks prior to enrolment.
             Before enrolment, these patients must have their qualifying echocardiography and/or
             cardiac MRI examination at least 12 weeks after the event.

          7. Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve
             repair/replacement.

          8. Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.

          9. Probable alternative or concomitant diagnoses which in the opinion of the investigator
             could account for the patient's HF symptoms and signs (e.g. anaemia, hypothyroidism).

         10. Body mass index >50 kg/m2.

        Further exclusion criteria may apply