DAPA-RESIST
Research type
Research Study
Full title
DAPA-RESIST - Sodium glucose cotransporter-2 inhibitor DAPAgliflozin versus thiazide diuretic in patients with heart failure and diuretic RESISTance: a multi-centre, open-label, randomised controlled clinical trial
IRAS ID
281882
Contact name
John McMurray
Contact email
Sponsor organisation
NHS Greater Glasgow and Clyde
Eudract number
2020-004832-48
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 0 days
Research summary
Diuretic resistance is defined as failure to achieve effective decongestion despite appropriate or escalating loop diuretic doses. Diuretic resistance has a high prevalence amongst patients with decompensated heart failure, is difficult to treat and is associated with adverse outcomes including prolonged hospital stay and increased mortality.
Current treatment guidelines involve adding a second diuretic agent (thiazide or thiazide-like diuretic or spironolactone which is a mineralocorticoid receptor antagonist) to the loop diuretic. These second diuretic agents have shown limited efficacy in achieving adequate diuresis and decongestion in diuretic resistant patients.
Dapagliflozin has proven cardiovascular and renal benefits in clinical trials amongst patients with impaired cardiac function and impaired renal function. The reason for this is unclear, but we suspect that a diuretic effect of the drug (the drug makes patients pass more urine) may partly explain its benefit.
We have designed a comprehensive clinical trial to study if dapagliflozin is more effective in promoting diuresis in patients with diuretic resistance, compared to metolazone (a thiazide-like diuretic). This study will be carried out in three secondary care hospitals that cover the entire population of Greater Glasgow and two sites in England.
A total of 80 eligible inpatients with heart failure and reduced ejection fraction (HFrEF) and up to an additional 40 inpatients with heart failure and preserved ejection fraction (HFpEF) will be recruited (n=120). Eligible patients will be randomised 1:1 to either dapagliflozin 10mg once daily or metolazone 5 or 10mg once daily for up to 3 consecutive days.
Participants will be followed-up daily until 96 hours for main endpoints and at hospital discharge for safety endpoints. Post-trial follow-up: until 90 days from discharge for exploratory and safety endpoints.
We will measure weight, blood and urine tests, electrocardiogram (record electrical activity of the heart), ultrasound (heart, lungs) and ask patients to complete validated questionnaires.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
20/EE/0289
Date of REC Opinion
17 Dec 2020
REC opinion
Favourable Opinion