CTRI/2025/04/085641 [Registered on: 25/04/2025] Trial Registered Prospectively
Last Modified On:
21/11/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical study to determine the efficacy and safety of finerenone with SGLT2 inhibitor versus standard of care on morbidity and mortality among hospitalized heart failure patients
Scientific Title of Study
COmbiNed eFfIcacy and safety of an eaRly, intensive
MAnagement sTrategy with fInerenOne and SGLT2 iNhibitor in patients hospitalized with Heart Failure(CONFIRMATION-HF)
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
202303CPC version no.3 dated 10-Sep-2024
Protocol Number
NCT06024746
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Vijay Kumar Chopra
Designation
Senior Director
Affiliation
Max Super Speciality Hospital
Address
Max Super Speciality Hospital,Department of Cardiology,Heart Failure and Clinical Research,Saket (East block)- A unit of Devki Devi Foundation,2,Press Enclave Road,Saket,New Delhi
Brazil Canada China India Spain Sri Lanka United Kingdom United States of America
Sites of Study
No of Sites = 8
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Mohammad Mohamodullah Razi
Ganesh Shankar Vidyarthi Memorial Medical College
Department of Cardiology,3rd floor,Swaroop Nagar, Kanpur, Uttar Pradesh-208002 Kanpur Nagar UTTAR PRADESH
7408427786
drmmrazi@gmail.com
Dr Kamal H Sharma
Matis Multispeciality Hospital
Department of Interventional Cardiology,OPD No.2,Opposite Adani CNG Gas Station, Near Motera BRTS Bus Stop,Cross Roads, Motera, Ahmedabad, Gujarat - 380005 Ahmadabad GUJARAT
9426020154
kamalsharma1975@rediffmail.com
Dr Vijay Kumar Chopra
Max Super Speciality Hospital
Department of Clinical Cardiology,Heart failure and Research,1st floor, near Cath labs,A unit of Devki Devi Foundation, 2,Press enclave road,Saket,New Delhi-110017 New Delhi DELHI
9650896800
vijay.chopra@maxhealthcare.com
Dr Shantanu Sengupta
Sengupta Hospital and Research Institute
Department of Cardiology Research,3rd floor,Room No.1,Ravinagar Square, Amravati Road, Nagpur, Maharashtra - 440033 Nagpur MAHARASHTRA
9923190925
senguptasp@gmail.com
Dr Ramya Das N K
Sree Chitra Tirunal Institute for Medical Sciences and Technology
Department of Cardiology,2nd floor,Room No.1212,Jai Nagar W Road, Chalakkuzhi, Thiruvananthapuram Kerala - 695011 Thiruvananthapuram KERALA
8281641327
ramyadasnk@gmail.com
Dr Jitendra Pal Singh Sawhney
Sri Ganga Ram Hospital
Department of Cardiology,5th Floor,Rajinder Nagar, New Delhi - 110060 New Delhi DELHI
9810059773
jpssawhney@yahoo.com
Dr Sandeep Bansal
Vardhman Mahavir Medical College and Safdarjung Hospital
Department of Cardiology,7th floor,Room No.754,Ring Road Ansari Nagar, New Delhi,South Delhi - 110029 South DELHI
9810543368
drsbansal2000@yahoo.com
Dr Jagadish H R
Victoria Hospital, Bangalore Medical College and Research Institute
Department of Cardiology,2nd floor,Room No.47c,PMSSY,City Market, Bangalore-560002 Bangalore KARNATAKA
Ethics Committee of BMCRI, Bangalore Medical College and Research Institute
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee SCTIMST
Submittted/Under Review
Institutional Ethics Committee VMMC And SAFDARJUNG HOSPITAL
Submittted/Under Review
Shakti Hospital Ethics Committee
Approved
Sir Gangaram Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: I50||Heart failure,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Finerenone and Empagliflozin
Finerenone dosing is based on worldwide labeling based on comprehensive safety data from Phase 3 studies in approximately 13000 patients and the regime used in the Phase 3 FINEARTS-HF trial, with the goal of providing the optimal benefit to risk profile across the range of eGFR based on experience in the development program. The starting dose of Finerenone will depend up the GFR value at baseline and will be titrated up or down based on eGFR and potassium values.Based on previous observations, the expected change in steady state serun potassium following administartion of Finerenone 10,20 and 40mg once daily in patients with HF is an increase of 0.1,0.2 and 0.2mmol/L and a decrease in eGFR by 2.4,3.1 and 3.8 mL/min/1.73m square respectively.
Empagliflozin dose is based on the approved prescribing information.
The study has a fixed treatment duration of 6 months for each participant. Once daily oral administration of 10 mg, 20 mg, or 40 mg of finerenone in combination with empagliflozin 10 mg daily is the intervention strategy.
Comparator Agent
Standard of care
Participants hospitalized for Heart Failure in the standard of care arm will be managed by their usual care providers who will receive a summary of HF guideline recommendations.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Provide electronic or written informed consent , either personally or through a legally authorized representative (LAR) as permitted by local regulations.
2. Age greater than or equal to 18 years or legal age of majority if greater than 18 years in the participants country of residence.
3. Current hospitalization or recently discharged (within 10 days prior to screening) with the primary diagnosis of HF.
4. Heart failure signs and symptoms at the time of hospital admission, including
a.Symptoms (at least one of the following) persistent dyspnea at rest or with minimal exertion worse than baseline or new or worsening orthopnea, and
b.Signs of fluid overload (at least one of the following) congestion on chest X-ray, rales on chest auscultation, clinically relevant edema caused by HF (as judged by the investigator), elevated jugular venous pressure
5.Elevated N terminal pro B type natriuretic peptide (NTproBNP) greater than or equal to 500 pg per mL or Btype natriuretic peptide (BNP) greater than or equal to 125 pg per mL according to the local lab for patients in sinus rhythm or elevated NTproBNP greater than or equal to 1500 pg per mL or BNP greater than 375 pg per mL for patients with atrial fibrillation (AF), measured during the current hospitalization or in the 72 hours prior to hospital admission. (Note for patients treated with an angiotensin receptor neprilysin inhibitor [ARNI] in the previous 4 weeks prior to randomization, only NTproBNP values should be used.)
6.Fulfillment of the following stabilization criteria (if randomized during hospitalization)
a.Systolic BP greater than or equal to 100 mmHg and no symptoms of hypotension in the 6 hours prior to randomization.
b.No increase in intravenous diuretic dose for 6 hours prior to randomization.
c.No intravenous vasodilators, including nitrates, within the last 6 hours prior to randomization.
d.No intravenous inotropic drugs or mechanical circulatory support for 24 hours prior to randomization
7.Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic (eg furosemide, torsemide, bumetanide).
8.Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study
ExclusionCriteria
Details
1.Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis.
2.Documented prior history of severe hyperkalemia (potassium greater than or equal to 6.0 mmol per L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use.
3.Treatment with non steroidal MRA (finerenone, esaxerenone, apararenone), steroidal MRA (spironolactone, eplerenone, canrenone), or SGLT2i within 30 days prior to randomization treatment with steroidal or non-steroidal MRA or SGLT2i should not be interrupted for the purpose of enrollment into the study.
4.eGFR less than 30 mL per min per 1.73m square and or potassium less than 5.0 mmol per L at screening.
5.Acute MI, coronary revascularization, valve replacement or repair, or implantation of a cardiac resynchronization therapy device within 30 days prior to randomization. (Note pacemakers or implantable cardioverter defibrillators without resynchronization function are allowed.)
6.Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial (according to investigator judgement) or currently using or plan for mechanical circulatory support eg left ventricular assist device, intra-aortic balloon pump, or patients on mechanical ventilation or patients with planned outpatient inotropic support.
7.Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of HF. (Note secondary mitral regurgitation or tricuspid regurgitation due to dilated cardiomyopathy is not excluded unless planned for surgery or intervention during the course of the study.)
8.Cardiomyopathy due to known acute inflammatory heart disease (eg acute myocarditis within 90 days prior to randomization), infiltrative diseases (eg amyloidosis), accumulation diseases (eg haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (eg stress cardiomyopathy), known hypertrophic obstructive cardiomyopathy, complex (according to investigator s judgement) congenital heart disease, or known pericardial constriction.
9.Probable alternative cause of participant s HF symptoms that, in the opinion of the investigator, primarily accounts for patient s symptoms specifically, patients with severe pulmonary disease requiring home oxygen or chronic oral steroid therapy, primary pulmonary arterial hypertension at screening.
10.Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (eg itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (eg efavirenz, phenobarbital), or potent CYP3A4 inducers (eg carbamazepine, phenytoin, St. John s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period.
11.Known hypersensitivity to the IP (active substance or excipients).
12.Any other condition or therapy (eg breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency [Child Pugh C], Addison s disease, or other severe condition as per investigator s judgment such as disease with less than 1 year life expectancy) which would make the participant unsuitable for this study and not allow participation for the full planned study period.
13.Concurrent participation in another interventional clinical study using an investigational agent (eg not approved for any indication) within 30 days prior to randomization
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
1. Time to all cause mortality
2. Number of total HF events (first and recurrent hospitalization or urgent outpatient visit for HF)
3. Time to first HF event
4. Kansas City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) change from baseline to 6 months of 5 points or greater assessed by the win-ratio method.
5. Serious Adverse events
6. Adverse events leading to discontinuation of IP.
Ongoing, up to 18 months
Secondary Outcome
Outcome
TimePoints
KCCQ-TSS, mean change from baseline to 6 months
6 months
Time to first occurrence of all-cause mortality or HF event (hospitalization for HF or urgent visit due to HF)
Ongoing, up to 18 months
Total (first and recurrent) HF events from baseline to 90 days
90 days
Target Sample Size
Total Sample Size="125" Sample Size from India="125" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
09/06/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
09/07/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 3 randomized, controlled, open label study which compares two management strategies in patients with an acute episode of decompensated HF: an early, intensive strategy of finerenone initiated simultaneously with a sodium-glucose co-transporter inhibitor (SGLT2i) versus standard of care.
Since Finerenone has demonstrated to reduce the risk of sustained estimated glomerular filtration rate decline, end stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in patients with chronic kidney disease associated with type 2 diabetes, it’s combination with SGLT2i class of drugs -which are also recommended to reduced HF hospitalization and CV mortality in patients with HFrEF with or without diabetes and have been shown to lower the combined risk of worsening HF or CV death in patients with HF. Hence establishing that early initiation of combination therapy with finerenoneand SGLT2iis well tolerated and can improve clinical outcomes thatcould have a practice changing impact.
Patients will be screened based on the inclusion/exclusion criteria and will be randomly allocated (1:1) to standard of care management or an early, intensive management strategy including empagliflozin 10 mg daily and finerenone once daily at a starting dose of 10 or 20 or 40 mg based on their local laboratory eGFR at baseline.
Outcome will be assessed based on the Primary objective: whether a strategy of early, intensive combination therapy with finerenone and empagliflozin provides superior clinical outcomes compared with local standard of care in patients with HHF., Secondary objective: whether early, intensive combination therapy can reduce all-cause mortality and total HF events (first and recurrent), improve KCCQ-TSS (at 6 months) and reduce HF events (at 90 days) and the Safety objective: by assessing the occurrence of AEs with finerenone and empagliflozin compared with standard of care.
The analysis of the endpoints will be performed as per the Statistical Analysis Plan and Safety Analysis Set.