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

  • STATUS
    Recruiting
  • End date
    Oct 30, 2022
  • participants needed
    120
  • sponsor
    NHS Greater Glasgow and Clyde
Updated on 7 May 2021

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.

Description

The investigators aim to assess whether SGLT2i (in addition to IV loop diuretic) results in greater diuresis and decongestion compared to the standard practice of treatment with the thiazide-like diuretic metolazone (in addition to IV loop diuretic) in patients hospitalised for heart failure, with both renal impairment and diuretic resistance. Dapagliflozin has received National Institute for Health and Care Excellence (NICE) approval as an add-on option to optimised standard care in patients with HFrEF. The investigators primary focus is patients with HFrEF as it is in ambulatory patients with this phenotype that SGLT2 inhibition has already been shown to reduce morbidity and mortality (DAPA-HF).However, the investigators will also enrol patients with HFpEF in an ancillary study as they present the same management challenges as patients with HFrEF and the study hypothesis and aims are as clinically relevant in HFpEF as in HFrEF. HFpEF patients in the ancillary study will undergo the same protocol as the main study. One recent trial demonstrating benefit of a SGLT1/2 inhibitor, the Effect of Sotagliflozin on Cardiovascular Events in Patients With Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF), included patients with both HFrEF and HFpEF hospitalised with worsening heart failure (NCT03521934). This trial demonstrated similar efficacy of sotagliflozin on cardiovascular death and worsening heart failure in patients with a LVEF <50% and 50%.There are other large trials currently underway specifically with SGLT2i in ambulatory patients with HFpEF underway. These trials are either fully recruited, or close to full enrolment. Both already have extensive follow-up of several thousand patients and are due to complete follow up in the next 1-2 years (EMPEROR-Preserved and DELIVER). Therefore, the findings will be contemporaneous and complementary to the results of those trials.

Details
Condition Heart failure, Heart disease, Congestive Heart Failure, Cardiac Disease, cardiac failure, congestive heart disease
Treatment Dapagliflozin 10 MG Oral Tablet, Metolazone Tablets
Clinical Study IdentifierNCT04860011
SponsorNHS Greater Glasgow and Clyde
Last Modified on7 May 2021

Eligibility

Yes No Not Sure

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
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