Home » Trials » SLCTR/2024/022


RandomizEd trial to DEtermine the efficacy and safety of FINErenone on morbidity and mortality among heart failure patients with left ventricular ejection fraction greater than or equal to 40% hospitalized due to an episode of acute decompensated Heart Failure (REDEFINE-HF)

-

SLCTR Registration Number

SLCTR/2024/022


Date of Registration

04 Jul 2024

The date of last modification

Jul 05, 2024



Application Summary


Scientific Title of Trial

RandomizEd trial to DEtermine the efficacy and safety of FINErenone on morbidity and mortality among heart failure patients with left ventricular ejection fraction greater than or equal to 40% hospitalized due to an episode of acute decompensated Heart Failure (REDEFINE-HF)


Public Title of Trial

A study to determine the efficacy and safety of finerenone versus placebo on morbidity and mortality among hospitalized heart failure patients (REDEFINE-HF)


Disease or Health Condition(s) Studied

Heart Failure


Scientific Acronym

REDEFINE-HF


Public Acronym

REDEFINE-HF


Brief title

Assessing the safety and efficacy on finerenone among hospitalized heart failure patients


Universal Trial Number

U1111-1307-5956


Any other number(s) assigned to the trial and issuing authority

ClinicalTrials.gov Identifier: NCT06008197 EudraCT: 2023-508581-15-00 (ERC, FoM, UoK)


Trial Details


What is the research question being addressed?

Is finerenone effective and safe compared to placebo in reducing the occurrence of total (first and subsequent) heart failure (HF) events and cardiovascular (CV) death among patients hospitalized with acute decompensated Heart Failure with mild-range Ejection Fraction/Heart Failure with Preserved Ejection Fraction (HFmrEF/HFpEF)?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded : Participants, Investigators, Healthcare providers, Outcome assessors


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 3


Intervention(s) planned

Study sites: The National Hospital of Sri Lanka, Colombo North Teaching Hospital, Sri Jayewardenepura General Hospital, Kandy National Hospital, District General Hospital Polonnaruwa, Colombo South Teaching Hospital, Jaffna Teaching Hospital, Negombo District General Hospital, General Sir John Kotelawala Defence University

Randomisation: Participants will be randomly assigned to treatment groups based on a computer-generated randomization schedule prepared before the study by or under the supervision of the sponsor statistician or delegate. Randomization will be balanced by using randomly permuted blocks for each site and stratified by country.

Intervention: Patients will be randomly allocated (1:1) to receive one finerenone or matching placebo tablet orally each day. The dose will be adjusted based on the patient’s kidney function and serum/plasma potassium. The starting dose of finerenone or placebo will depend on the local laboratory eGFR value at baseline. The investigator will titrate the dose of study intervention once the participant has been on a stable dose for 30±7 days. Participants who do not tolerate their starting dose of 20 mg may be down titrated at any point during the study, including between scheduled visits if required for safety reasons. Up titration of dose may be performed from Day 30 onward at any scheduled or unscheduled contact. eGFR and serum/plasma potassium will be checked 28±7 days after dose adjustment and at any other time deemed appropriate by the investigator. Patients will be instructed to take one tablet of study medication at approximately the same time each day, with a glass of water with or without food. Tablets containing 10 mg and 20 mg finerenone will differ in size from 40 mg finerenone tablets, but will be identical in appearance (size, shape, color) to matching placebo tablets. The packaging and labelling will be designed to maintain the blinding of the investigator’s team and the participants. The placebo tablet is active-free tablet and contains lactose.


Inclusion criteria

• Males and females age >=18 years • Current hospitalization or recently discharged with the primary diagnosis of heart failure • Heart failure signs and symptoms at the time of hospital admission • Imaging evidence of mildly reduced or preserved left ventricular ejection fraction (EF) (40% or higher) • Elevated N-terminal pro B-type natriuretic peptide (NTproBNP) >=1000 pg/mL or B-type natriuretic peptide (BNP) >=250 pg/mL for patients without atrial fibrillation (AF); or elevated NTproBNP >=2000 pg/mL or BNP >=500 pg/mL for patients with AF


Exclusion criteria

• Treatment with a mineralocorticoid receptor antagonist (MRA) • Documented prior history of severe hyperkalemia in the setting of MRA use • Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73m² or serum/plasma potassium >5.0 mmol/L at screening • Acute myocardial infarction, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days • Hemodynamically significant (severe) uncorrected primary cardiac valvular disease • Cardiomyopathy due to known acute inflammatory heart, infiltrative diseases, accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, known hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or known pericardial constriction • Probable alternative cause of participant's heart failure symptoms • Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or moderate CYP3A4 inducers, or potent CYP3A4 inducers



Primary outcome(s)

1.

Composite total of HF events and CV death. (Total (first and subsequent) HF hospitalizations, urgent visits for worsening HF, and CV deaths with finerenone compared to placebo).

[

Ongoing, up to 30 months

]
2.

Number of serious adverse events.

The expected adverse drug events are hyperkalemia, hypotension, impairment of kidney function, hyperuricemia, and hyponatremia

[

Ongoing, up to 30 months

]
3.

Number of adverse events leading to discontinuation of study drug.

The expected adverse drug events are hyperkalemia, hypotension, impairment of kidney function, hyperuricemia, and hyponatremia

[

Ongoing, up to 30 months

]

Secondary outcome(s)

1.

Time to first occurrence of the composite of CV death or HF event

[

Ongoing, up to30 months

]
2.

Change from baseline in the Total Symptom Score on the Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) at Month 6

[

6 months

]
3.

Time to CV death

[

Ongoing, up to 30 months

]
4.

Total HF events

[

Ongoing, up to 30 months

]
5.

Time to death from any cause

[

Ongoing, up to 30 months

]
6.

Total hospitalizations for any cause

[

Ongoing, up to 30 months

]
7.

Total number of days alive and out of the hospital

[

Ongoing, up to 30 months

]
8.

Number of patients with sustained decrease in eGFR ≥40% relative to baseline

[

Ongoing, up to 30 months

]
9.

Number of patients with sustained eGFR <15 ml/min/1.73 m^2

[

Ongoing, up to 30 months

]
10.

Number of patients requiring initiation of dialysis or renal transplant.

[

Ongoing, up to 30 months

]

Target number/sample size

216 (108 in a group)


Countries of recruitment

Argentina, Australia, Brazil, Canada, Croatia, Czech Republic, Germany, Greece, Hungary, India, Italy, Korea, Democratic People's Republic of, Lithuania, Malaysia, Peru, Poland, Spain, Sri Lanka, Taiwan, Province of China, United Kingdom, United States


Anticipated start date

2024-09-01


Anticipated end date

2026-09-30


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Bayer AG


Regulatory approvals

Pending



State of Ethics Review Approval


Status

Approved


Date of Approval

2023-07-11


Approval number

P/24/02/2024


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address:P.O Box 6, Thalagolla Road, Ragama, Sri Lanka
Telephone:+94 11 2961267
Email: erckelaniya@gmail.com

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. Gamini Galappatthy
Consultant Cardiologist
Institute of Cardiology, National Hospital of Sri Lanka, Colombo 10
-
+94777604200
-
gamini_galappatthy@hotmail.com
-

Contact Person for Public Queries

Dr. Gamini Galappatthy
Consultant Cardiologist
Institute of Cardiology, National Hospital of Sri Lanka, Colombo 10
-
+94777604200
-
gamini_galappatthy@hotmail.com
-


Primary study sponsor/organization

CPC Clinical Research

2115 N Scranton Street #2040, Aurora, CO, USA 80045 Phone number: 303-860-9900
info@cpcmed.org


Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description

N/A


Study protocol available

No


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results