202301CPC Redefine-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

8 Oct 2024 → ongoing

Decision date (initial)

2024-08-09

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: Safety, Efficacy

To determine whether finerenone reduces total (first and subsequent) HF events and CV death compared with placebo in patients hospitalized with acute decompensated HFmrEF/HFpEF.

Secondary objectives 1

1. To determine the effects of finerenone compared with placebo on clinical events and change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS).

Conditions and MedDRA coding

Heart condition

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 (during or within 30 days of discharge) 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 b. Signs of fluid overload (at least one of the following): congestion on chest X-ray, rales on chest auscultation, clinically relevant edema (as judged by the investigator), elevated jugular venous pressure
4. 5. Imaging evidence of mildly reduced or preserved EF (40% or higher) per local reading on the most recent assessment, preferably measured during current hospitalization; a historical left ventricular EF (LVEF) assessment may be used if there is no in-hospital measurement and if it was measured within 12 months prior to screening provided there was no major intervening event affecting EF such as an MI
5. 6. 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 without atrial fibrillation (AF); or elevated NTproBNP ≥1500 pg/mL or BNP ≥375 pg/mL for patients with AF, measured during the current hospitalization, in the 72 hours prior to hospital admission, or during the 30 days 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).
6. 7. Fulfillment of the following stabilization criteria (if randomized during hospitalization): a. Systolic blood pressure (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
7. 8. Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic, e.g. furosemide, torsemide, bumetanide
8. 9. 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
9. 1. Provide written informed consent.

Exclusion criteria 13

1. 1. Currently on or planned for long-term therapy with an MRA (finerenone, spironolactone, eplerenone, canrenone, esaxerenone); treatment with MRA should not be interrupted for the purpose of enrollment into the study. (Note: patients with recent MRA exposure should not be randomized/receive study treatment until 7 days from the last dose to allow adequate washout).
2. 10. 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
3. 12. Any other condition or therapy (e.g., breastfeeding, cardiogenic shock, clinically overt severe hepatic insufficiency, 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.
4. 13. Participation in another interventional clinical study or treatment with another investigational medicine or device within 30 days prior to randomization
5. 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.
6. 3. eGFR <25 mL/min/1.73m² or potassium >5.0 mmol/L at screening.
7. 4. 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).
8. 5. 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 planned for palliative care for HF, 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
9. 6. Hemodynamically significant (severe) uncorrected primary cardiac valvular disease considered by the investigator to be the primary cause of heart failure (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)
10. 7. 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
11. 8. 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
12. 9. 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.
13. 11. Known hypersensitivity to the IP (active substance or excipients).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary study endpoint is a composite of total (first and subsequent) HF events (HF hospitalization or urgent visit for worsening HF) and CV death.

Secondary endpoints 1

1. Secondary endpoints include treatment group difference in: 1.Time to first occurrence of the composite of CV death or HF event; 2. Total HF events; 3. Change from baseline to month 6 in KCCQ-TSS; 4. Time to CV death 5. Time to death from any cause

Investigational products

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

Test 3

Placebo 1

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 3

Sponsor responsibilities

Article 77 compliance

Colorado Prevention Center

Article 77 implementation

Colorado Prevention Center

Locations

11 EU/EEA countries · 129 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 108 files

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

Application history

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