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

Last updated: April 6, 2023
Sponsor: NHS Greater Glasgow and Clyde
Overall Status: Active - Not Recruiting

Phase

3

Condition

Hyponatremia

Chest Pain

Congestive Heart Failure

Treatment

N/A

Clinical Study ID

NCT04860011
GN19CA407
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Male or female ≥18 years of age
  • Informed consent
  • Primary reason for admission to hospital is worsening HF meeting the European Societyof Cardiology (ESC) definition.14
  • Diuretic Resistance as defined as: Lack of weight loss or absence of a negative fluidbalance (as defined above) over the preceding 24 hours despite treatment with highdose 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 ascitesand/or elevated jugular venous pressure, and/or radiographic or ultrasonic evidence ofpulmonary congestion
  • Expected hospital length of stay >3 days

Exclusion

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 obstructivenephropathy, contrast induced nephropathy, or acute tubular necrosis
  • Enrollment in another randomised clinical trial involving medical or device-basedinterventions (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 theexcipients
  • Hypertrophic obstructive cardiomyopathy (HOCM) or significant valvular disease inwhom surgical or percutaneous repair or replacement may be considered.
  • SGLT2i, thiazide or thiazide-like diuretics administration in the previous 48hours prior to randomisation
  • Active genital tract infections
  • Anyone who, in the investigators' opinion, is not suitable to participate in thetrial for other reasons

Study Design

Total Participants: 61
Study Start date:
April 27, 2021
Estimated Completion Date:
April 03, 2023

Study 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.

Connect with a study center

  • Glasgow Royal Infirmary

    Glasgow, Strathclyde G4 0SF
    United Kingdom

    Site Not Available

  • Queen Elizabeth University Hospital

    Glasgow, Strathclyde G51 4TF
    United Kingdom

    Site Not Available

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