DAPAgliflozin Versus Thiazide Diuretic in Patients With Heart Failure and Diuretic RESISTance

• Status: Recruiting
• Trial end date: 2022-10-30
• Target enrollment: 0
• Participant gender: All

Summary

To assess the effect of dapagliflozin compared with metolazone, added to furosemide, on diuresis and decongestion in hospitalised heart failure patients with diuretic resistance, and renal impairment. The primary analysis will be in patients with HFrEF but patients with HFpEF will also be recruited in an ancillary study and included in supplementary analyses.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NHS Greater Glasgow and Clyde
• Collaborator: University of Glasgow
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin; Metolazone

Criteria

Inclusion Criteria:

• Male or female ≥18 years of age

• Informed consent

• Primary reason for admission to hospital is worsening HF meeting the European Society of Cardiology (ESC) definition.14

• Diuretic Resistance as defined as: Lack of weight loss or absence of a negative fluid balance (as defined above) over the preceding 24 hours despite treatment with high dose IV loop diuretic (equivalent of ≥160mg IV furosemide in 24 hours)

• Plasma BNP ≥ 100 pg/mL or plasma NT-proBNP ≥ 400 pg/mL in current hospital admission

• eGFR <60 ml/min/1.73m2 required within 24 hours before randomisation

• Ongoing clinical evidence of congestion: pitting peripheral oedema and/or ascites and/or elevated jugular venous pressure, and/or radiographic or ultrasonic evidence of pulmonary congestion

• Expected hospital length of stay >3 days

Exclusion Criteria:

• Inability to give informed consent e.g. due to significant cognitive impairment

• Intravascular volume depletion based on investigator's clinical assessment

• eGFR <20 mL/min/1.73 m2

• Alternative explanation for worsening renal function such as obstructive nephropathy, contrast induced nephropathy, or acute tubular necrosis

• Enrollment in another randomised clinical trial involving medical or device-based interventions (co-enrolment in observational studies is permitted)

• Women of child-bearing potential

• History of allergy to SGLT2i or thiazide or thiazide-like diuretics or any of the excipients

• Hypertrophic obstructive cardiomyopathy (HOCM) or significant valvular disease in whom surgical or percutaneous repair or replacement may be considered.

• SGLT2i, thiazide or thiazide-like diuretics administration in the previous 48 hours prior to randomisation

• Active genital tract infections

• Anyone who, in the investigators' opinion, is not suitable to participate in the trial for other reasons