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

NCT04860011 | Unknown Phase 3 DMC

• 1 other identifier: GN19CA407
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 2

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (3)

• Diuretic effect

  Diuretic effect, as assessed by mean change in weight

  from randomisation to 48 hours

• Diuretic effect

  Diuretic effect, as assessed by mean change in weight

  from randomisation to 72 hours

• Diuretic effect

  Diuretic effect, as assessed by mean change in weight

  from randomisation to 96 hours

Secondary Outcomes (9)

• Change in congestion measured by ultrasound

  from randomisation to 48 hours

• Change in congestion measured by ultrasound

  from randomisation to 72 hours

• Change in congestion measured by ultrasound

  from randomisation to 96 hours

• Loop diuretic efficiency

  from randomisation to 48 hours

• Loop diuretic efficiency

  from randomisation to 72 hours

Other Outcomes (48)

• Change in urinary spot sodium

  from randomisation to 48 hours

• Change in urinary spot sodium

  from randomisation to 72 hours

• Change in urinary spot sodium

  from randomisation to 96 hours

Study Arms (2)

SGLT2i

EXPERIMENTAL

Sodium-glucose Co-transporter-2 inhibitors

Drug: Dapagliflozin 10 MG Oral Tablet

Thiazide

EXPERIMENTAL

Thiazide or thiazide like diuretic

Drug: Metolazone Tablets

Interventions

Dapagliflozin 10 MG Oral Tablet DRUG

Dapagliflozin 10mg once daily

Also known as: dapagliflozin

SGLT2i

Metolazone Tablets DRUG

Metolazone 5MG or 10MG once daily

Also known as: metolazone

Thiazide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• NHS Greater Glasgow and Clyde: lead
• University of Glasgow: collaborator

Study Sites (2)

Glasgow Royal Infirmary

Glasgow, Strathclyde, G4 0SF, United Kingdom

Location

Queen Elizabeth University Hospital

Glasgow, Strathclyde, G51 4TF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37210742 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

dapagliflozin; Metolazone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• John McMurray, MBChB

  University of Glasgow and NHS Greater Glasgow and Clyde

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective, randomised, active-comparator, multi-centre, open label study.

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 26, 2021
• Study Start: April 27, 2021
• Primary Completion: October 30, 2022
• Study Completion: April 3, 2023
• Last Updated: April 10, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)