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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)

Treatments: Drug: Dapagliflozin; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03877237

2018-003442-16 (EudraCT Number)

D169EC00002

Details and patient eligibility

About

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)

Enrollment: 313 patients

Sex: All

Ages: 18 to 150 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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313 participants in 2 patient groups, including a placebo group

Dapagliflozin

Experimental group

Description:

Green, diamond shaped, film coated tablets 10 mg administered orally, once daily

Treatment:

Drug: Dapagliflozin

Placebo

Placebo Comparator group

Description:

Green, diamond shaped, film coated tablets placebo administered orally, once daily

Treatment:

Other: Placebo