Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List (ARCADIA-HF)

August 3, 2023 updated by: Hospices Civils de Lyon

Acute Reno-Cardiac Action of Dapagliflozin In Advanced Heart Failure Patients on Heart Transplant Waiting List: a Multicenter, Double-blind, Randomized Clinical Trial.

In the DAPA-HF trial, the use of dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), reduced significantly the risk of worsening heart failure or death from cardiovascular causes compared to placebo among patients with heart failure (HF) and a reduced ejection fraction. This new drug offers a very potent and interesting therapeutic pathway since it reduces clinical congestion, it preserves glomerular renal function, does not appear to cause symptomatic clinical hypotension and improves symptoms and quality of life compared to placebo.

Advanced heart failure patients with reduced ejection fraction represent a small and severe subgroup of heart failure of patients with frequent worsening heart failure events and high rates of death. The effect of dapagliflozin in this subgroup of patients was not assessed in the DAPA-HF study. The therapeutic profile of SGLT2 inhibitors appears to be of high interest, since this group of patients has a poor tolerance to usual heart failure drugs, frequent worsening renal function and congestive symptoms persistence with poor quality of life scores.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a signaling glycoprotein considered to be involved in the pathogenesis of kidney disease. It is associated with the risk of acute kidney injury in different clinical and experimental situation. It is also a new validated biomarker predictive of adverse clinical outcome in heart failure patients. This biomarker allows a better risk stratification in heart failure patients after adjustment for Nt-proBNP.

As a useful biomarker implicated in both heart failure and acute kidney injury, suPAR seems to be an interesting biomarker to assess cardio-renal benefits of dapagliflozin.

The aim of this study is to investigate if a treatment by dapagliflozin reduces significantly suPAR compared to placebo in a population of advanced heart failure patients, candidates to heart transplantation. The effect of dapagliflozin compared to placebo will also be assessed on other secondary heart failure outcomes in this patient population.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

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.

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

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 2

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

  • France
      • Bron, France, 69677
        • Hôpital Pneumologique et Cardiovasculaire Louis Pradel

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient has signed informed consent form
  2. Age ≥ 18 years
  3. NYHA class ≥3
  4. LVEF ≤ 35%
  5. On optimal medical management (OMM) based on current heart failure practice guidelines at maximal tolerated dose for at least 30 days
  6. On waiting list for heart transplantation after multidisciplinary Heart Team decision, with anticipated access to heart transplant ≥ 6 months

Exclusion Criteria:

  1. Priority patient on waiting list for heart transplantation
  2. Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy
  3. Inotrope dependent, existence of ongoing mechanical circulatory support
  4. Current acute decompensated HF or hospitalization due to decompensated HF <30 days prior to the enrolment
  5. History of any organ transplant or prior implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization
  6. Presence of an active, uncontrolled infection
  7. Any recent interventional procedure likely to improve symptoms and heart failure status (coronary revascularization, percutaneous mitral valve intervention, cardiac resynchronization therapy) < 60 days
  8. Glomerular filtration rate < 30 ml/min/1.73 m2, according to CKD-EPI formula
  9. Unstable or rapidly progressing renal disease
  10. Patients with severe hepatic impairment (Child-Pugh class C)
  11. Chronic treatment with dapagliflozin or other SGLT2 inhibitors
  12. Patient with known history of severe drug intolerance to dapagliflozin or any excipients of the dapagliflozin (galactose, lactase)
  13. Type 1 diabetes mellitus
  14. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators' discretion
  15. Participation in another clinical interventional trial
  16. Any condition other than heart failure that could limit survival to less than 24 months
  17. Positive pregnancy test if of childbearing potential or refusal to use adequate contraception or women breast-feeding
  18. Patients with any legal protection measure
  19. Patients without any health coverage
  20. Psychiatric disease/disorder, irreversible cognitive dysfunction or psychological issues that are likely to impair compliance

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: Triple

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.
Placebo Comparator: Control group
Drug: Placebo
Patients randomized in the control group will receive during 6 months, placebo once daily per oral route, in addition to the optimal medical management based on current heart failure practice guidelines.
Experimental: Treatment group Daplagliflozin
Drug: Dapagliflozin 10mg
The intervention group will receive, during 6 months, dapagliflozin per oral route at a dose of 10 mg once daily in addition to the optimal medical management based on current heart failure practice guidelines.

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
Time Frame
Levels of suPAR (ng/ml)
Time Frame: 6 months
6 months

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
VO2 max assessment
Time Frame: 6 months
VO2 max assessment to evaluate the functional status
6 months
cardiac output assessed by right heart catheterization
Time Frame: 6 months
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
6 months
pulmonary capillary wedge pressure assessed by right heart catheterization
Time Frame: 6 months
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
6 months
pulmonary artery systolic and mean pressure assessed by right heart catheterization
Time Frame: 6 months
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
6 months
mean pressure assessed by right heart catheterization
Time Frame: 6 months
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
6 months
right atrial pressure assessed by right heart catheterization
Time Frame: 6 months
The impact of dapagliflozin on hemodynamic parameters between baseline and 6 months assessed by right heart catheterization hemodynamic parameters
6 months
Left Ventricular Ejection Function assessed by echocardiography
Time Frame: 6 months
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
6 months
Left ventricular end-diastolic diameter assessed by echocardiography
Time Frame: 6 months
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
6 months
Left ventricular end systolic volume assessed by echocardiography
Time Frame: 6 months
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
6 months
mitral regurgitation grade assessed by echocardiography
Time Frame: 6 months
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
6 months
left atrial volume assessed by echocardiography
Time Frame: 6 months
The impact of dapagliflozin on echocardiographic parameters between baseline and 6 months
6 months
Nt-proBNP level
Time Frame: 6 months
6 months
Creatinine level
Time Frame: 6 months
6 months
Quality of life assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time Frame: 6 months
6 months

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.
Hospices Civils de Lyon

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.
  • Principal Investigator: Guillaume BAUDRY, Dr, Hospices Civils de Lyon

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 (Estimated)

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.
September 1, 2022

Primary Completion (Estimated)

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.
April 1, 2024

Study Completion (Estimated)

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 1, 2024

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).
March 1, 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.
March 3, 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.
March 4, 2021

Study Record Updates

Last Update Posted (Actual)

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.
August 7, 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.
August 3, 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.
August 1, 2023

More Information

Terms related to this study

Keywords

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.
  • 69HCL20_1135
  • 2020-005713-40 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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