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Heart FailurePhase 3DAPARESISTNCT04860011

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

A Phase 3 study testing Dapagliflozin 10 MG Oral Tablet and Metolazone Tablets in people with Heart Failure, run by NHS Greater Glasgow and Clyde at 2 sites in United Kingdom.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure
What is being tested?
Dapagliflozin 10 MG Oral Tablet and Metolazone Tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
2 sitesUnited Kingdom
Study dates
27 Apr 2021to 3 Apr 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Glasgow Royal Infirmary

    Glasgow, Strathclyde, G4 0SF

  • Queen Elizabeth University Hospital

    Glasgow, Strathclyde, G51 4TF

Other trials in United Kingdom

About this study

Official title: 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

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.

Read the 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
Being tested
Dapagliflozin 10 MG Oral Tablet, Metolazone Tablets
Medical subject headings
Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dapagliflozin 10 MG Oral TabletDrug

    Also called dapagliflozin

    Dapagliflozin 10mg once daily

  • Metolazone TabletsDrug

    Also called metolazone

    Metolazone 5MG or 10MG once daily

Study groups in NCT04860011
Study groupRoleWhat they receive
SGLT2iExperimentalSodium-glucose Co-transporter-2 inhibitors
Receives: Drug: Dapagliflozin 10 MG Oral Tablet
ThiazideExperimentalThiazide or thiazide like diuretic
Receives: Drug: Metolazone Tablets

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Diuretic effect

    Diuretic effect, as assessed by mean change in weight

    Measured: from randomisation to 48 hours

  2. Diuretic effect

    Diuretic effect, as assessed by mean change in weight

    Measured: from randomisation to 72 hours

  3. Diuretic effect

    Diuretic effect, as assessed by mean change in weight

    Measured: from randomisation to 96 hours

Secondary outcomes (9)

  1. Change in congestion measured by ultrasound

    Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones

    Measured: from randomisation to 48 hours

  2. Change in congestion measured by ultrasound

    Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones

    Measured: from randomisation to 72 hours

  3. Change in congestion measured by ultrasound

    Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones

    Measured: from randomisation to 96 hours

  4. Loop diuretic efficiency

    Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.

    Measured: from randomisation to 48 hours

  5. Loop diuretic efficiency

    Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.

    Measured: from randomisation to 72 hours

  6. Loop diuretic efficiency

    Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.

    Measured: from randomisation to 96 hours

  7. Change in ADVOR clinical congestion score

    Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested

    Measured: from randomisation to 48 hours

  8. Change in ADVOR clinical congestion score

    Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested

    Measured: from randomisation to 72 hours

  9. Change in ADVOR clinical congestion score

    Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested

    Measured: from randomisation to 96 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2021
  2. Study start27 Apr 2021
  3. Primary completion30 Oct 2022
  4. Study completion3 Apr 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective, randomised, active-comparator, multi-centre, open label study.
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04860011
Sponsor's protocol ID
GN19CA407
Acronym
DAPARESIST
Status last verified
Apr 2023
First submitted
6 Apr 2021
Last updated
10 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: To be discussed and agreed at TSC

Publications

  • 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.

    PubMed 37210742

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dapagliflozin 10 MG Oral Tablet and Metolazone Tablets in people with Heart Failure, run by NHS Greater Glasgow and Clyde at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Diuretic effect (time frame: from randomisation to 48 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04860011, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2023.

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