DAPAgliflozin Versus Thiazide Diuretic in Patients With Heart Failure and Diuretic RESISTance (DAPARESIST)

April 6, 2023 updated by: NHS Greater Glasgow and Clyde

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United Kingdom
    • Strathclyde
      • Glasgow, Strathclyde, United Kingdom, G4 0SF
        • Glasgow Royal Infirmary
      • Glasgow, Strathclyde, United Kingdom, G51 4TF
        • Queen Elizabeth University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: SGLT2i
Sodium-glucose Co-transporter-2 inhibitors
Drug: Dapagliflozin 10 MG Oral Tablet
Dapagliflozin 10mg once daily
Other Names:
  • dapagliflozin
Experimental: Thiazide
Thiazide or thiazide like diuretic
Drug: Metolazone Tablets
Metolazone 5MG or 10MG once daily
Other Names:
  • metolazone

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Diuretic effect
Time Frame: from randomisation to 48 hours
Diuretic effect, as assessed by mean change in weight
from randomisation to 48 hours
Diuretic effect
Time Frame: from randomisation to 72 hours
Diuretic effect, as assessed by mean change in weight
from randomisation to 72 hours
Diuretic effect
Time Frame: from randomisation to 96 hours
Diuretic effect, as assessed by mean change in weight
from randomisation to 96 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in congestion measured by ultrasound
Time Frame: from randomisation to 48 hours
Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones
from randomisation to 48 hours
Change in congestion measured by ultrasound
Time Frame: from randomisation to 72 hours
Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones
from randomisation to 72 hours
Change in congestion measured by ultrasound
Time Frame: from randomisation to 96 hours
Change in congestion, assessed using lung ultrasound as a measure of the sum of B-lines across 8 zones
from randomisation to 96 hours
Loop diuretic efficiency
Time Frame: from randomisation to 48 hours
Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.
from randomisation to 48 hours
Loop diuretic efficiency
Time Frame: from randomisation to 72 hours
Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.
from randomisation to 72 hours
Loop diuretic efficiency
Time Frame: from randomisation to 96 hours
Loop diuretic efficiency will be defined as weight loss in kilograms divided by furosemide equivalents in milligrams.
from randomisation to 96 hours
Change in ADVOR clinical congestion score
Time Frame: from randomisation to 48 hours
Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested
from randomisation to 48 hours
Change in ADVOR clinical congestion score
Time Frame: from randomisation to 72 hours
Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested
from randomisation to 72 hours
Change in ADVOR clinical congestion score
Time Frame: from randomisation to 96 hours
Change in ADVOR clinical congestion score will be measured on a scale of 0 to 10 with 0 being the least congested
from randomisation to 96 hours

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in urinary spot sodium
Time Frame: from randomisation to 48 hours
change in urinary spot urine measured in mmol/L
from randomisation to 48 hours
Change in urinary spot sodium
Time Frame: from randomisation to 72 hours
change in urinary spot urine measured in mmol/L
from randomisation to 72 hours
Change in urinary spot sodium
Time Frame: from randomisation to 96 hours
change in urinary spot urine measured in mmol/L
from randomisation to 96 hours
Change in NT-proBNP
Time Frame: from randomisation to 48 hours
measured in pg/ml
from randomisation to 48 hours
Change in NT-proBNP
Time Frame: from randomisation to 72 hours
measured in pg/ml
from randomisation to 72 hours
Change in NT-proBNP
Time Frame: from randomisation to 96 hours
measured in pg/ml
from randomisation to 96 hours
Change in serum uric acid
Time Frame: from randomisation to 48 hours
measured in umol/L
from randomisation to 48 hours
Change in serum uric acid
Time Frame: from randomisation to 72 hours
measured in umol/L
from randomisation to 72 hours
Change in serum uric acid
Time Frame: from randomisation to 96 hours
measured in umol/L
from randomisation to 96 hours
Total net fluid loss
Time Frame: from randomisation to 48 hours
difference between fluid intake and output measured in ml
from randomisation to 48 hours
Total net fluid loss
Time Frame: from randomisation to 72 hours
difference between fluid intake and output measured in ml
from randomisation to 72 hours
Total net fluid loss
Time Frame: from randomisation to 96 hours
difference between fluid intake and output measured in ml
from randomisation to 96 hours
Change in dyspnoea
Time Frame: from randomisation to 48 hours
Change in dyspnoea (breathlessness) measured using a 7 point Likert scale (1= strong positive to 7 = strong negative) and a 11-point Dyspnoea Numerical Rating scale (0= not breathless at all to 10=breathlessness as bad as you can imagine)
from randomisation to 48 hours
Change in dyspnoea
Time Frame: from randomisation to 72 hours
Change in dyspnoea (breathlessness) measured using a 7 point Likert scale (1= strong positive to 7 = strong negative) and a 11-point Dyspnoea Numerical Rating scale (0= not breathless at all to 10=breathlessness as bad as you can imagine)
from randomisation to 72 hours
Change in dyspnoea
Time Frame: from randomisation to 96 hours
Change in dyspnoea (breathlessness) measured using a 7 point Likert scale (1= strong positive to 7 = strong negative) and a 11-point Dyspnoea Numerical Rating scale (0= not breathless at all to 10=breathlessness as bad as you can imagine)
from randomisation to 96 hours
Patient global assessment
Time Frame: from randomisation to 48 hours
Change in patients perception of their own health measured using a 7 point Likert scale (1= strong positive to 7 = strong negative)
from randomisation to 48 hours
Patient global assessment
Time Frame: from randomisation to 72 hours
Change in patients perception of their own health measured using a 7 point Likert scale (1= strong positive to 7 = strong negative)
from randomisation to 72 hours
Patient global assessment
Time Frame: from randomisation to 96 hours
Change in patients perception of their own health measured using a 7 point Likert scale (1= strong positive to 7 = strong negative)
from randomisation to 96 hours
Time from randomisation to discharge
Time Frame: through study completion, an average of 5 days
Time from randomisation to discharge measured in hours
through study completion, an average of 5 days
In-hospital mortality
Time Frame: through study completion, an average of 5 days
Number of patients who died in hospital
through study completion, an average of 5 days
Serum uric acid ≥360 μmol/L
Time Frame: from randomisation to 48 hours
measured in umol/L
from randomisation to 48 hours
Serum uric acid ≥360 μmol/L
Time Frame: from randomisation to 72 hours
measured in umol/L
from randomisation to 72 hours
Serum uric acid ≥360 μmol/L
Time Frame: from randomisation to 96 hours
measured in umol/L
from randomisation to 96 hours
change in serum glucose
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
change in serum glucose
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
change in serum glucose
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours
Rate of heart failure re-hospitalisation or death
Time Frame: through study completion (on average 5 days) and up to 90 days
Number of patients who are re-admitted to hospital after initial discharge
through study completion (on average 5 days) and up to 90 days
Change in serum creatinine
Time Frame: from randomisation to 48 hours
measured in umol/L
from randomisation to 48 hours
Change in serum creatinine
Time Frame: from randomisation to 72 hours
measured in umol/L
from randomisation to 72 hours
Change in serum creatinine
Time Frame: from randomisation to 96 hours
measured in umol/L
from randomisation to 96 hours
increase in serum creatinine concentration
Time Frame: from randomisation to 48 hours
measured in umol/L
from randomisation to 48 hours
increase in serum creatinine concentration
Time Frame: from randomisation to 72 hours
measured in umol/L
from randomisation to 72 hours
increase in serum creatinine concentration
Time Frame: from randomisation to 96 hours
measured in umol/L
from randomisation to 96 hours
change in blood urea (nitrogen)
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
change in blood urea (nitrogen)
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
change in blood urea (nitrogen)
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours
change in serum potassium
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
change in serum potassium
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
change in serum potassium
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours
Serum potassium <3.5 mmol/L and ≥5.5 mmol/L
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
Serum potassium <3.5 mmol/L and ≥5.5 mmol/L
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
Serum potassium <3.5 mmol/L and ≥5.5 mmol/L
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours
change in serum sodium
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
change in serum sodium
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
change in serum sodium
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours
Serum sodium concentration <125 mmol/L
Time Frame: from randomisation to 48 hours
measured in mmol/L
from randomisation to 48 hours
Serum sodium concentration <125 mmol/L
Time Frame: from randomisation to 72 hours
measured in mmol/L
from randomisation to 72 hours
Serum sodium concentration <125 mmol/L
Time Frame: from randomisation to 96 hours
measured in mmol/L
from randomisation to 96 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NHS Greater Glasgow and Clyde

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Glasgow

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: John McMurray, MBChB, University of Glasgow and NHS Greater Glasgow and Clyde

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 27, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2022

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 3, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 6, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 26, 2021

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 10, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 6, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GN19CA407

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

To be discussed and agreed at TSC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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