Principal Investigator: John  Ryan
Keywords: heart failure , drug study Department: Cardiovascular Medicine
IRB Number: 00139554
Specialty: Cardiology, Cardiology
Sub Specialties: General Cardiology, Heart Failure
Recruitment Status: Not yet recruiting

Contact Information

Jeff Gibbs
jeffrey.gibbs@hsc.utah.edu
801-587-4877

Brief Summary

Primary:

1. To demonstrate the superiority of finerenone to placebo in reducing the rate of the composite CV endpoint.

Composite primary endpoint:

 Cardiovascular (CV) death and total (first and recurrent) heart failure (HF) events (hospitalizations for heart failure [HHF] or urgent HF visits) in HF patients (New York Heart Association [NYHA] class II–IV) and LVEF ≥40%.

Secondary:

2. To determine the superiority of finerenone to placebo for each secondary endpoint

3. To assess the safety and tolerability of finerenone

Secondary endpoints:

· Change from baseline to Month 6, 9 and 12 in Total Symptom Score (TSS) of the KCCQ

· Time to first occurrence of composite renal endpoint: sustained decrease in estimated glomerular filtration rate (eGFR) ≥40%relative to baseline over at least 4 weeks, or sustained eGFR decline <15ml/min/1.73m2 or initiation of dialysis or renal transplantation.

· Time to all-cause mortality

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:

Age

1. Participant must be aged 40 years and older, at the time of signing the informed

consent.

Type of Participant and Disease Characteristics:

2. Diagnosis of heart failure with NYHA class II–IV, ambulatory or hospitalized

primarily for heart failure (if a hospitalized patient cannot be randomized as an

in-patient, randomization as soon as possible after discharge is encouraged)

3. On diuretic treatment for at least 30 days prior to randomization. 

4. Documented LVEF of ≥40% measured by any modality within the last 12 months, at the latest at screening; if several values are available, the most recent one shall be reported. If LVEF was not measured in the past 12 months, a new measurement may be done at screening

5. Structural heart abnormalities based on any local imaging measurement within the last

12 months, latest at screening, defined by at least 1 of the following findings:

o LAD ≥3.8cm, LAA ≥20cm2, LAVI >30 mL/m2, LVMI ≥115 g/m2 (♂) /

95 g/m2 (♀), septal thickness or posterior wall thickness ≥1.1 cm

6. NT-proBNP ≥300 pg/mL (BNP ≥100 pg/mL) in sinus rhythm or

NT-proBNP ≥900pg/mL (BNP ≥300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown; see Section 4.1) for participants 1 obtained at the following time:

o Within 90 days prior to randomization if patient had been hospitalized for HF

requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization

OR

o Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days.

 

Sex

7. Male or female.

Women of childbearing potential can only be included in the study if a pregnancy

test is negative at screening and baseline and if they agree to use adequate

contraception which is consistent with local regulations regarding the methods for

contraception for those participating in clinical trials.

 

Informed Consent

8. Capable of giving signed informed consent as described in Section 10.1.3 which

includes compliance with the requirements and restrictions listed in the informed

consent form (ICF) and in this protocol.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

1. eGFR <25 mL/min/1.73 m² at either screening or randomization visit.

NOTE: one reassessment of eGFR is allowed at the screening and randomization visit, respectively

2. Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit.

NOTE: one reassessment of potassium is allowed at the screening and randomization visit, respectively

3. Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to

randomization

4. Myocardial infarction or any event which could have reduced the ejection fraction

within 90 days prior to randomization

5. Coronary artery bypass graft surgery in the 90 days prior to randomization

6. Percutaneous coronary intervention in the 30 days prior to randomization

7. Stroke or transient ischemic cerebral attack within 90 days prior to randomization

8. Probable alternative cause of participants’ HF symptoms that in the opinion of the

investigator primarily accounts for patient’s dyspnea such as significant pulmonary

disease, anemia or obesity. Specifically, patients with the below are excluded:

· Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy

· History of primary pulmonary arterial hypertension

· Hemoglobin <10 g/dl

· Valvular heart disease considered by the investigator to be clinically significant

· Body mass index (BMI) >50 kg/m2 at screening

9. Systolic blood pressure (SBP) ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at randomization

10. Life-threatening or uncontrolled arrhythmias at screening and/or randomization

including but not limited to sustained ventricular tachycardia and atrial fibrillation,

or atrial flutter with resting ventricular rate >110 bpm

11. Symptomatic hypotension with mean systolic blood pressure <90 mmHg at screening or at randomization

12. Any primary cause of HF scheduled for surgery, e.g. valve disease such as severe aortic stenosis or severe mitral regurgitation by the time of screening or randomization

13. History of peripartum cardiomyopathy, chemotherapy induced cardiomyopathy,

viral myocarditis, right heart failure in absence of left-sided structural disease,

pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative

cardiomyopathy including amyloidosis

14. Presence of left ventricular assist device by the time of screening or randomization

15. History of hyperkalemia or acute renal failure during MRA treatment for

>7 consecutive days, leading to permanent discontinuation of the MRA treatment

16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotrophin urine or serum test

17. Known hypersensitivity to the study intervention (active substance or excipients)

18. Hepatic insufficiency classified as Child-Pugh C at screening or randomization

19. Addison’s disease.

 

Prior/Concomitant Therapy

20. Requirement of any IV vasodilating drug (e.g. nitrates, nitroprusside), any IV

natriuretic peptide (e.g. nesiritide, carperitide), any IV positive inotropic agents, or

mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical

ventilation, or any ventricular assist device) within 24 hours prior to randomization

21. Participants who require treatment with more than one ACEI, ARB or

angiotensin-receptor neprilysin inhibitor (ARNI), or two simultaneously at

randomization

22. Continuous (at least 90 days) treatment with an MRA (e.g. spironolactone, eplerenone, canrenone, esaxerenone) within 12 months prior to screening. Last intake at least 30 days before randomization. Treatment with MRA should not be interrupted with

the purpose of enrollment into the study

23. Concomitant treatment with any renin inhibitor or potassium-sparing diuretic that cannot be stopped prior to randomization and for the duration of the treatment period

24. Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or inducers that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) and/or the moderate CYP3A4 inhibitor erythromycin, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period. 

Other Exclusions

25. Any other condition or therapy, which would make the participant unsuitable for this study and will not allow participation for the full planned study period (e.g. active malignancy or other condition limiting life expectancy to less than 12 months)

26. Previous assignment to treatment during this study

27. Participation in another interventional clinical study (e.g. Phase 1 to 3 clinical studies) or treatment with another investigational medicinal product within 30 days prior to randomization

28. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site)

29. Known current alcohol and/or illicit drug abuse that may interfere with the participant’s safety and/or compliance at the discretion of the investigator

30. Participant is in custody by order of an authority or a court of law.

31. For sites following the DCT model only: participant is not willing or able to use the smartphone/app required for DCT elements.