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

NCT ID: NCT04860011

Last Updated: 2023-04-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2023-04-03

Brief 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.

Detailed 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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SGLT2i

Sodium-glucose Co-transporter-2 inhibitors

Group Type: EXPERIMENTAL

Dapagliflozin 10 MG Oral Tablet

Intervention Type: DRUG

Dapagliflozin 10mg once daily

Thiazide

Thiazide or thiazide like diuretic

Group Type: EXPERIMENTAL

Metolazone Tablets

Intervention Type: DRUG

Metolazone 5MG or 10MG once daily

Interventions

Dapagliflozin 10 MG Oral Tablet

Dapagliflozin 10mg once daily

Intervention Type: DRUG

Metolazone Tablets

Metolazone 5MG or 10MG once daily

Intervention Type: DRUG

Other Intervention Names

dapagliflozin; metolazone

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Glasgow

OTHER

Sponsor Role: collaborator

NHS Greater Glasgow and Clyde

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John McMurray, MBChB

Role: STUDY_CHAIR

University of Glasgow and NHS Greater Glasgow and Clyde

Locations

Glasgow Royal Infirmary

Glasgow, Strathclyde, United Kingdom

Queen Elizabeth University Hospital

Glasgow, Strathclyde, United Kingdom

Countries

United Kingdom

References

Yeoh SE, Osmanska J, Petrie MC, Brooksbank KJM, Clark AL, Docherty KF, Foley PWX, Guha K, Halliday CA, Jhund PS, Kalra PR, McKinley G, Lang NN, Lee MMY, McConnachie A, McDermott JJ, Platz E, Sartipy P, Seed A, Stanley B, Weir RAP, Welsh P, McMurray JJV, Campbell RT. Dapagliflozin vs. metolazone in heart failure resistant to loop diuretics. Eur Heart J. 2023 Aug 14;44(31):2966-2977. doi: 10.1093/eurheartj/ehad341.

Reference Type: DERIVED

PMID: 37210742 (View on PubMed)

Other Identifiers

GN19CA407

Identifier Type: -

Identifier Source: org_study_id