ARETHA: cARdiomems vEriciguaT Heart fAilure (A double-blind randomized placebo-controlled trial of vericiguat in heart failure patients with CardioMEMS™ HF System)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

6 Dec 2024 → 17 Mar 2026

Decision date (initial)

2024-09-20

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bayer AG · Novo Nordic Foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Investigate the effect of vericiguat in patients with heart failure with reduced ejection fraction (HFrEF)

Secondary objectives 1

1. To evaluate the NT-proBNP reducing effect of vericiguat compared with placebo

Conditions and MedDRA coding

Heart failure with reduced ejection fraction (HFrEF)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 18 years or older
2. Ability to provide informed consent
3. CardioMEMS implanted for clinical indication (≥ 2 weeks prior to first visit)
4. Known chronic heart failure (HF) with left ventricular ejection fraction (LVEF) <45% (documented within the past 24 months by an imaging modality: echocardiography, nuclear imaging, LV angiography, or magnetic resonance imaging)
5. NYHA functional class II-IV symptoms.
6. Optimal and stable medical therapy for HF (as indicated under point 5 of exclusion criteria)
7. Systolic blood pressure (SBP) ≥100 mmHg
8. Diastolic pulmonary artery pressure (dPAP) >15 mmHg more than 8 days in the last 14 days on the CardioMEMS system.

Exclusion criteria 29

1. Patients in optimization phase in the CardioMEMS system or implantation of the CardioMEMs device within the past 2 weeks
2. Recent (within 14 days) hospitalization for decompensated HF
3. Average supine SBP <100 mmHg at the screening or randomization visit
4. Current symptomatic hypotension
5. Recent changes (within 48 hours) in diuretic dose, recent (within 4 weeks) initiation of hydralazine, long-acting nitrates, β-blockers, ACEi/ARB or ARNi.
6. Marked variability in PA diastolic pressure during screening period
7. Low CardioMEMS reading compliance (<75% 30 days reading compliance)
8. Concurrent or anticipated use of (1) long-acting nitrates or nitric oxide (NO) doners including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine, (2) sGC stimulators such as riociguat, (3) PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil or (4) intravenous inotropes
9. Previous or planned LVAD or HTx implantation
10. Implantation of CRT device within the previous 90 days
11. Known allergy or sensitivity to any sGC stimulator
12. Primary valvular heart disease requiring surgery or intervention or is within 3 months after valvular surgery or intervention
13. Diagnosed with hypertrophic obstructive cardiomyopathy, acute myocarditis, amyloidosis, sarcoidosis, or takotsubo cardiomyopathy
14. Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia
15. Acute coronary syndrome (unstable angina, non-ST elevation myocardial infarction [NSTEMI], or ST elevation myocardial infarction [STEMI] or coronary revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) within 60 days, or indication for coronary revascularization at first study visit
16. Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days
17. Complex congenital heart disease
18. Active endocarditis or constrictive pericarditis
19. eGFR <15 mL/min/1.73 m2 or chronic dialysis
20. Severe hepatic insufficiency such as with hepatic encephalopathy
21. Malignancy or other non-cardiac condition limiting life expectancy to <1 years
22. Require continuous home oxygen for severe pulmonary disease
23. Current alcohol and/or drug abuse
24. Participating in another interventional clinical study or plans to participate in any other trial/investigation during the duration of this study
25. Mental or legal incapacitation and is unable to provide informed consent
26. Immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is involved with this study
27. Interstitial Lung Disease
28. Pregnant or breastfeeding (or lactating) or plans to become pregnant or to breastfeed during the course of the study
29. Women of reproductive age and childbearing potential not using at least one safe form of contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the diastolic pulmonary artery pressure (dPAP) lowering effect of vericiguat in comparison to placebo

Secondary endpoints 1

1. To evaluate the NT-proBNP reducing effect of vericiguat compared with placebo

Investigational products

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

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Sponsor and principal investigator

Public contact point

Organisation

Rigshospitalet

Contact name

Sponsor and principal investigator

Third parties 3

Locations

1 EU/EEA country · 3 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 11 files

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

Application history

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