A Study to Determine the Efficacy and Safety of Finerenone and SGLT2i in Combination in Hospitalized Patients With Heart Failure (CONFIRMATION-HF)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Colorado Prevention Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

2 Dec 2025 → ongoing

Decision date (initial)

2025-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine whether a strategy of usual care plus early, intensive combination therapy with finerenone and an SGLT2i provides superior clinical outcomes (defined as a hierarchical composite of all-cause mortality, heart failure events, and ≥5 point difference in change from baseline for Kansas City Cardiomyopathy Questionnaire – Total Symptom Score [KCCQ-TSS]) compared with local usual care in patients hospitalized with heart failure.

Secondary objectives 1

1. To determine whether usual care plus early, intensive combination therapy with finerenone and an SGLT2i can reduce time to first occurrence of all-cause mortality or HF events (hospitalization for HF or urgent visit due to HF), improve KCCQ-TSS (at 6 months), and reduce HF events at 90 days.

Conditions and MedDRA coding

Heart condition

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 2. Age ≥18 years or legal age of majority if >18 years in the participant’s country of residence.
2. 3. Current hospitalization or recently discharged with a primary diagnosis of acute HF.
3. 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.
4. 5. Elevated N-terminal pro B-type natriuretic peptide (NTproBNP) ≥500 pg/mL or B-type natriuretic peptide (BNP) ≥125 pg/mL according to the local lab for patients in sinus rhythm; or elevated NTproBNP ≥1500 pg/mL or BNP ≥375 pg/mL for patients with atrial fibrillation (AF), measured during the current hospitalization, in the 72 hours prior to hospital admission, or during the XY post-discharge. (Note: for patients treated with an angiotensin receptor neprilysin inhibitor [ARNI] in the previous 4 weeks prior to randomization, NTproBNP values should be used where available.)
5. 6. Fulfillment of the following stabilization criteria (if randomized during hospitalization): a. Systolic BP ≥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.
6. 7. Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic (e.g., furosemide, torsemide, bumetanide).
7. 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 effective contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study.
8. 1. Provide written informed consent.

Exclusion criteria 13

1. Diagnosis of type 1 diabetes or prior history of diabetic ketoacidosis.
2. Documented prior history of severe hyperkalemia (potassium ≥6.0 mmol/L and/or resulting in hospitalization or Emergency Department visit) in the setting of MRA use.
3. Currently on or planned for long-term therapy with non-steroidal MRA (finerenone, esaxerenone, apararenone, balcinrenone), steroidal MRA (spironolactone, eplerenone, canrenone), or SGLT2i. Potential participants should not have MRA or SGLT2i stopped for the purpose of enrollment into the study. Patients with recent MRA exposure should not be randomized or receive study treatment until 7 days from the last dose to allow adequate washout.
4. eGFR <30 mL/min/1.73m² and/or potassium >5.0 mmol/L at screening.
5. Acute MI due to plaque rupture, coronary revascularization, valve replacement/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, e.g., 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 (e.g., acute myocarditis within 90 days prior to randomization), infiltrative diseases (e.g., amyloidosis), accumulation diseases (e.g., haemochromatosis, Fabry disease), muscular dystrophies, cardiomyopathy with reversible causes (e.g., 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 (e.g., itraconazole, ritonavir, indinavir, cobicistat, clarithromycin), or moderate CYP3A4 inducers (e.g., efavirenz, phenobarbital), or potent CYP3A4 inducers (e.g., carbamazepine, phenytoin, St. John’s Wort) that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period. (Note: a list of excluded CYP3A4 inhibitors and inducers is provided in Appendix D.) Concomitant treatment with renin inhibitor, more than one angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or ARNI, or with a potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period.
11. Known hypersensitivity to finerenone or empagliflozin (active substance or excipients).
12. Any other condition or therapy (e.g., 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 <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 (e.g., not approved for any indication) within 30 days or 5 half-lives of the other study intervention, whichever is longer, prior to randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is clinical benefit, defined as a hierarchical composite endpoint of: 1. Time to all-cause mortality 2. Number of total HF events 3. Time to first HF event 4. KCCQ-TSS change from baseline to 6 months of 5 points or greater assessed by the win-ratio method

Secondary endpoints 1

1. Secondary endpoints include treatment group difference in: • KCCQ-TSS, mean change from baseline to 6 months • Time to first occurrence of all-cause mortality or HF event (hospitalization for HF or urgent visit due to HF) • Total (first and recurrent) HF events from baseline to 90 days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Colorado Prevention Center

Sponsor organisation

Colorado Prevention Center

Address

2115 Scranton Street Suite 2040

City

Aurora

Postcode

80045-7120

Country

United States

Scientific contact point

Organisation

Colorado Prevention Center

Contact name

Marc Bonaca

Public contact point

Organisation

Colorado Prevention Center

Contact name

Marc Bonaca

Third parties 2

Sponsor responsibilities

Article 77 compliance

Colorado Prevention Center

Article 77 implementation

Colorado Prevention Center

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications