A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001)

NCT02861534 | Completed Phase 3 Results DMC

• 3 other identifiers: 1242-0012016-000671-25MK-1242-001
• Study Type: interventional
• Target: 5,050
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, placebo-controlled, parallel-group, multi-center, double-blind, event driven study of vericiguat (MK-1242) in participants with heart failure with reduced ejection fraction (HFrEF). The primary hypothesis is vericiguat (MK-1242) is superior to placebo in increasing the time to first occurrence of the composite of cardiovascular (CV) death or heart failure (HF) hospitalization in participants with HFrEF.

Conditions

Heart Failure; Chronic Heart Failure With Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization

  Time to First Occurrence of Composite Endpoint of CV Death or HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any HF hospitalization or CV death event at the time of analysis were censored at their last available information, the date of their non-CV death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A clinical events committee (CEC) reviewed and adjudicated the endpoint events. A time-to-event methodology was used to evaluate the results; the incidence rate of participants with an event (number of participants with an event per 100 participant-years at risk) is provided.

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Secondary Outcomes (9)

• Time to the First Occurrence of CV Death

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

• Time to the First Occurrence of HF Hospitalization

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

• Time to Total HF Hospitalizations (Including First and Recurrent Events)

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

• Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

• Time to All-Cause Mortality

  Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Study Arms (2)

Vericiguat

EXPERIMENTAL

Participants receive a starting dose of 2.5 mg of vericiguat taken orally once daily with food, on a background of HF standard of care. The vericiguat dose will be uptitrated to 5 mg and to 10 mg.

Drug: Vericiguat

Placebo

PLACEBO COMPARATOR

Participants receive a starting matching placebo dose of 2.5 mg taken orally once daily with food, on a background of HF standard of care. The matching placebo dose will be uptitrated to 5 mg and to 10 mg.

Drug: Placebo for vericiguat

Interventions

Vericiguat DRUG

2.5, 5.0, or 10.0 mg orally once daily

Also known as: MK-1242

Vericiguat

Placebo for vericiguat DRUG

2.5, 5.0, or 10.0 mg orally once daily

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of chronic HF (New York Heart Association \[NYHA\] Class II-IV) on standard therapy before qualifying HF decompensation
• Previous HF hospitalization within 6 months prior to randomization or intravenous (IV) diuretic treatment for HF (without hospitalization) within 3 months.
• Brain natriuretic peptide (BNP) levels: sinus rhythm-≥ 300 pg/mL; atrial fibrillation-≥ 500 pg/mL and N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) levels: sinus rhythm- ≥ 1000 pg/mL; atrial fibrillation - ≥ 1600 pg/mL within 30 days prior to randomization
• Left ventricular ejection fraction (LVEF) of \<45% assessed within 12 months prior to randomization by any method
• If female, is not of reproductive potential or agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: practice abstinence from heterosexual activity or use (or have her partner use) acceptable contraception during heterosexual activity.

You may not qualify if:

• Clinically unstable at the time of randomization as defined by either the administration of any IV treatment within 24 hours prior to randomization, and/or systolic blood pressure (SBP) \<100 mmHg or symptomatic hypotension
• Current or anticipated use of long-acting nitrates or nitric oxide (NO) donors including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine
• Current or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil
• Current use or anticipated use of a soluble guanylate cyclase (sGC) stimulator such as riociguat
• Known allergy or sensitivity to any sGC stimulator
• Awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), receiving continuous IV infusion of an inotrope, or has/anticipates receiving an implanted ventricular assist device
• Primary valvular heart disease requiring surgery or intervention, or is within 3 months after valvular surgery or intervention
• Hypertrophic obstructive cardiomyopathy
• Acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy
• Post-heart transplant cardiomyopathy
• Tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia
• 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 time of randomization
• Symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within 60 days
• Complex congenital heart disease
• Active endocarditis or constrictive pericarditis

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Bayer: collaborator
• Canadian VIGOUR Centre: collaborator
• Duke Clinical Research Institute: collaborator

Related Publications (23)

• Pieske B, Patel MJ, Westerhout CM, Anstrom KJ, Butler J, Ezekowitz J, Hernandez AF, Koglin J, Lam CSP, Ponikowski P, Roessig L, Voors AA, O'Connor CM, Armstrong PW; VICTORIA Study Group. Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial. Eur J Heart Fail. 2019 Dec;21(12):1596-1604. doi: 10.1002/ejhf.1664. Epub 2019 Dec 9.

  PMID: 31820546 RESULT

• Shah P, Zheng Y, Pieske B, Melenovsky V, Lam CSP, Sliwa K, Butler J, Ezekowitz JA, deFilippi CR, O'Connor CM, Sandhu RK, Roessig L, Tromp J, Westerhout CM, Voors AA, Armstrong PW; VICTORIA Study Group. Phenomapping in Heart Failure With Reduced Ejection Fraction to Identify Subpopulations With High Residual Risk: A VICTORIA Substudy. Circ Heart Fail. 2025 Oct 8:e013166. doi: 10.1161/CIRCHEARTFAILURE.125.013166. Online ahead of print.

  PMID: 41058565 DERIVED

• Khan MS, Butler J, Young R, Lewis BS, Escobedo J, Refsgaard J, Reyes E, Roessig L, Blaustein RO, Lam CSP, Voors AA, Ponikowski P, Anstrom KJ, Armstrong PW; VICTORIA Study Group. Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial. JACC Heart Fail. 2024 Oct;12(10):1750-1759. doi: 10.1016/j.jchf.2024.05.007. Epub 2024 Jun 26.

  PMID: 38934967 DERIVED

• Mentz RJ, Stebbins A, Butler J, Chiang CE, Ezekowitz JA, Hernandez AF, Hilkert R, Lam CSP, McDonald K, O'Connor CM, Pieske B, Ponikowski P, Roessig L, Sweitzer NK, Voors AA, Anstrom KJ, Armstrong PW; VICTORIA Study Group. Recurrent Hospitalizations and Response to Vericiguat in Heart Failure and Reduced Ejection Fraction. JACC Heart Fail. 2024 May;12(5):839-846. doi: 10.1016/j.jchf.2023.12.005. Epub 2024 Feb 14.

  PMID: 38363272 DERIVED

• Chew DS, Li Y, Bigelow R, Cowper PA, Anstrom KJ, Daniels MR, Davidson-Ray L, Hernandez AF, O'Connor CM, Armstrong PW, Mark DB; VICTORIA Study Group. Cost-Effectiveness of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: The VICTORIA Randomized Clinical Trial. Circulation. 2023 Oct 3;148(14):1087-1098. doi: 10.1161/CIRCULATIONAHA.122.063602. Epub 2023 Sep 6.

  PMID: 37671551 DERIVED

• Lam CSP, Pina IL, Zheng Y, Bonderman D, Pouleur AC, Saldarriaga C, Pieske B, Blaustein RO, Nkulikiyinka R, Westerhout CM, Armstrong PW; VICTORIA Study Group. Age, Sex, and Outcomes in Heart Failure With Reduced EF: Insights From the VICTORIA Trial. JACC Heart Fail. 2023 Sep;11(9):1246-1257. doi: 10.1016/j.jchf.2023.06.020. Epub 2023 Aug 9.

  PMID: 37565973 DERIVED

• Armstrong PW, Zheng Y, Lund LH, Butler J, Troughton RW, Emdin M, Lam CSP, Ponikowski P, Blaustein RO, O'Connor CM, Roessig L, Voors AA, Ezekowitz JA, Westerhout CM; VICTORIA Study Group. Evolution of NT-proBNP During Prerandomization Screening in VICTORIA: Implications for Clinical Outcomes and Efficacy of Vericiguat. Circ Heart Fail. 2023 Oct;16(10):e010661. doi: 10.1161/CIRCHEARTFAILURE.123.010661. Epub 2023 Jul 28.

  PMID: 37503602 DERIVED

• Ezekowitz JA, McMullan CJ, Westerhout CM, Pina IL, Lopez-Sendon J, Anstrom KJ, Hernandez AF, Lam CSP, O'Connor CM, Pieske B, Ponikowski P, Roessig L, Voors AA, Koglin J, Armstrong PW, Butler J; VICTORIA Study Group. Background Medical Therapy and Clinical Outcomes From the VICTORIA Trial. Circ Heart Fail. 2023 Sep;16(9):e010599. doi: 10.1161/CIRCHEARTFAILURE.123.010599. Epub 2023 Jul 7.

  PMID: 37417824 DERIVED

• Felker GM, North R, Mulder H, Jones WS, Anstrom KJ, Patel MJ, Butler J, Ezekowitz JA, Lam CSP, O'Connor CM, Roessig L, Hernandez AF, Armstrong PW; VICTORIA Study Group. Classification of Heart Failure Events by Severity: Insights From the VICTORIA Trial. J Card Fail. 2023 Aug;29(8):1113-1120. doi: 10.1016/j.cardfail.2023.04.015. Epub 2023 Jun 17.

  PMID: 37331690 DERIVED

• Butler J, Zheng Y, Khan MS, Bonderman D, Lund LH, deFilippi CR, Blaustein RO, Ezekowitz JA, Freitas C, Hernandez AF, O'Connor CM, Voors AA, Westerhout CM, Lam CSP, Armstrong PW; VICTORIA Study Group. Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA. JACC Heart Fail. 2023 May;11(5):583-592. doi: 10.1016/j.jchf.2022.12.014. Epub 2023 Apr 12.

  PMID: 37137660 DERIVED

• Armstrong PW, Zheng Y, Troughton RW, Lund LH, Zhang J, Lam CSP, Westerhout CM, Blaustein RO, Butler J, Hernandez AF, Roessig L, O'Connor CM, Voors AA, Ezekowitz JA; VICTORIA Study Group. Sequential Evaluation of NT-proBNP in Heart Failure: Insights Into Clinical Outcomes and Efficacy of Vericiguat. JACC Heart Fail. 2022 Sep;10(9):677-688. doi: 10.1016/j.jchf.2022.04.015. Epub 2022 Jul 6.

  PMID: 36049817 DERIVED

• Senni M, Lopez-Sendon J, Cohen-Solal A, Ponikowski P, Nkulikiyinka R, Freitas C, Vlajnic VM, Roessig L, Pieske B. Vericiguat and NT-proBNP in patients with heart failure with reduced ejection fraction: analyses from the VICTORIA trial. ESC Heart Fail. 2022 Dec;9(6):3791-3803. doi: 10.1002/ehf2.14050. Epub 2022 Jul 26.

  PMID: 35880474 DERIVED

• Senni M, Alemayehu WG, Sim D, Edelmann F, Butler J, Ezekowitz J, Hernandez AF, Lam CSP, O'Connor CM, Pieske B, Ponikowski P, Roessig L, Voors AA, Westerhout CM, McMullan C, Armstrong PW; VICTORIA Study Group. Efficacy and safety of vericiguat in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan: insights from the VICTORIA trial. Eur J Heart Fail. 2022 Sep;24(9):1614-1622. doi: 10.1002/ejhf.2608. Epub 2022 Jul 20.

  PMID: 35791083 DERIVED

• Butler J, Stebbins A, Melenovsky V, Sweitzer NK, Cowie MR, Stehlik J, Khan MS, Blaustein RO, Ezekowitz JA, Hernandez AF, Lam CSP, Nkulikiyinka R, O'Connor CM, Pieske BM, Ponikowski P, Spertus JA, Voors AA, Anstrom KJ, Armstrong PW; VICTORIA Study Group. Vericiguat and Health-Related Quality of Life in Patients With Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial. Circ Heart Fail. 2022 Jun;15(6):e009337. doi: 10.1161/CIRCHEARTFAILURE.121.009337. Epub 2022 Jun 3.

  PMID: 35656822 DERIVED

• Lam CSP, Mulder H, Lopatin Y, Vazquez-Tanus JB, Siu D, Ezekowitz J, Pieske B, O'Connor CM, Roessig L, Patel MJ, Anstrom KJ, Hernandez AF, Armstrong PW; VICTORIA Study Group. Blood Pressure and Safety Events With Vericiguat in the VICTORIA Trial. J Am Heart Assoc. 2021 Nov 16;10(22):e021094. doi: 10.1161/JAHA.121.021094. Epub 2021 Nov 6.

  PMID: 34743540 DERIVED

• Ezekowitz JA, Zheng Y, Cohen-Solal A, Melenovsky V, Escobedo J, Butler J, Hernandez AF, Lam CSP, O'Connor CM, Pieske B, Ponikowski P, Voors AA, deFilippi C, Westerhout CM, McMullan C, Roessig L, Armstrong PW. Hemoglobin and Clinical Outcomes in the Vericiguat Global Study in Patients With Heart Failure and Reduced Ejection Fraction (VICTORIA). Circulation. 2021 Nov 2;144(18):1489-1499. doi: 10.1161/CIRCULATIONAHA.121.056797. Epub 2021 Aug 25.

  PMID: 34432985 DERIVED

• Ezekowitz J, Mentz RJ, Westerhout CM, Sweitzer NK, Givertz MM, Pina IL, O'Connor CM, Greene SJ, McMullan C, Roessig L, Hernandez AF, Armstrong PW. Participation in a Heart Failure Clinical Trial: Perspectives and Opportunities From the VICTORIA Trial and VICTORIA Simultaneous Registry. Circ Heart Fail. 2021 Sep;14(9):e008242. doi: 10.1161/CIRCHEARTFAILURE.120.008242. Epub 2021 Aug 19.

  PMID: 34407626 DERIVED

• Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, Senni M, Butler J, Ezekowitz JA, Lam CSP, Pieske B, Ponikowski P, Voors AA, Anstrom KJ, Armstrong PW, O'connor CM, Hernandez AF; VICTORIA Study Group. Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial. J Card Fail. 2021 Jun 24:S1071-9164(21)00206-2. doi: 10.1016/j.cardfail.2021.05.016. Online ahead of print.

  PMID: 34217593 DERIVED

• Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, Senni M, Butler J, Ezekowitz JA, Lam CSP, Pieske B, Ponikowski P, Voors AA, Anstrom KJ, Armstrong PW, O'Connor CM; VICTORIA Study Group. Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial: VICTORIA Outcomes Model. J Card Fail. 2021 May 26:S1071-9164(21)00206-2. doi: 10.1016/j.cardfail.2021.05.016. Online ahead of print.

  PMID: 34216757 DERIVED

• Lam CSP, Giczewska A, Sliwa K, Edelmann F, Refsgaard J, Bocchi E, Ezekowitz JA, Hernandez AF, O'Connor CM, Roessig L, Patel MJ, Pieske B, Anstrom KJ, Armstrong PW; VICTORIA Study Group. Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event: Insights From the VICTORIA Trial. JAMA Cardiol. 2021 Jun 1;6(6):706-712. doi: 10.1001/jamacardio.2020.6455.

  PMID: 33185650 DERIVED

• Ezekowitz JA, O'Connor CM, Troughton RW, Alemayehu WG, Westerhout CM, Voors AA, Butler J, Lam CSP, Ponikowski P, Emdin M, Patel MJ, Pieske B, Roessig L, Hernandez AF, Armstrong PW. N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study. JACC Heart Fail. 2020 Nov;8(11):931-939. doi: 10.1016/j.jchf.2020.08.008. Epub 2020 Oct 7.

  PMID: 33039447 DERIVED

• Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, Hernandez AF, Butler J, Lam CSP, Ponikowski P, Voors AA, Jia G, McNulty SE, Patel MJ, Roessig L, Koglin J, O'Connor CM; VICTORIA Study Group. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2020 May 14;382(20):1883-1893. doi: 10.1056/NEJMoa1915928. Epub 2020 Mar 28.

  PMID: 32222134 DERIVED

• Armstrong PW, Roessig L, Patel MJ, Anstrom KJ, Butler J, Voors AA, Lam CSP, Ponikowski P, Temple T, Pieske B, Ezekowitz J, Hernandez AF, Koglin J, O'Connor CM. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial. JACC Heart Fail. 2018 Feb;6(2):96-104. doi: 10.1016/j.jchf.2017.08.013. Epub 2017 Oct 11.

  PMID: 29032136 DERIVED

MeSH Terms

Conditions

Heart Failure

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Mahesh J. Patel, MD

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

• Paul W. Armstrong, MD

  Canadian VIGOUR Centre - University of Alberta

  STUDY CHAIR

• Christopher M. O'Connor, MD

  Inova Heart and Vascular Institute

  PRINCIPAL INVESTIGATOR

• Burkert Pieske, MD

  Charité University Medicine and German Heart Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2016
• First Posted: August 10, 2016
• Study Start: September 20, 2016
• Primary Completion: June 18, 2019
• Study Completion: September 2, 2019
• Last Updated: November 15, 2021
• Results First Posted: June 29, 2020

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share