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

NCT04782245 | Withdrawn Phase 2 DMC

• 2 other identifiers: 69HCL20_11352020-005713-40
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

End-stage Heart Failure

Keywords

End-stage heart failure,; Cardio-renal syndrome; Dapagliflozin

Outcome Measures

Primary Outcomes (1)

• Levels of suPAR (ng/ml)

  6 months

Secondary Outcomes (14)

• VO2 max assessment

  6 months

• cardiac output assessed by right heart catheterization

  6 months

• pulmonary capillary wedge pressure assessed by right heart catheterization

  6 months

• pulmonary artery systolic and mean pressure assessed by right heart catheterization

  6 months

• mean pressure assessed by right heart catheterization

  6 months

Study Arms (2)

Treatment group Daplagliflozin

EXPERIMENTAL

Drug: Dapagliflozin 10mg

Control group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Dapagliflozin 10mg DRUG

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.

Treatment group Daplagliflozin

Placebo DRUG

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.

Control group

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Priority patient on waiting list for heart transplantation
• Etiology of heart failure due to or associated with uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis or restrictive cardiomyopathy
• Inotrope dependent, existence of ongoing mechanical circulatory support
• Current acute decompensated HF or hospitalization due to decompensated HF \<30 days prior to the enrolment
• History of any organ transplant or prior implantation of a ventricular assistance device (VAD) or similar device, or implantation expected after randomization
• Presence of an active, uncontrolled infection
• Any recent interventional procedure likely to improve symptoms and heart failure status (coronary revascularization, percutaneous mitral valve intervention, cardiac resynchronization therapy) \< 60 days
• Glomerular filtration rate \< 30 ml/min/1.73 m2, according to CKD-EPI formula
• Unstable or rapidly progressing renal disease
• Patients with severe hepatic impairment (Child-Pugh class C)
• Chronic treatment with dapagliflozin or other SGLT2 inhibitors
• Patient with known history of severe drug intolerance to dapagliflozin or any excipients of the dapagliflozin (galactose, lactase)
• Type 1 diabetes mellitus
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or extraction of study drug at investigators' discretion
• Participation in another clinical interventional trial

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Pneumologique et Cardiovasculaire Louis Pradel

Bron, 69677, France

Location

MeSH Terms

Conditions

Cardio-Renal Syndrome

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Heart Failure; Heart Diseases; Cardiovascular Diseases

Study Officials

• Guillaume BAUDRY, Dr

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 4, 2021
• Study Start: September 1, 2022
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: August 7, 2023

Record last verified: 2023-08

Locations

FR (1)