Heart FailurePhase 3VICTORIANCT02861534
A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001)
A Phase 3 study testing Vericiguat in people with Heart Failure and Chronic Heart Failure With Reduced Ejection Fraction, run by Merck Sharp & Dohme LLC.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Chronic Heart Failure With Reduced Ejection Fraction
- What is being tested?
- Vericiguat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,050 participants
- Where
- No sites listed yet
- Study dates
- 20 Sep 2016to 2 Sep 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 25Show fewer
- 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
- Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 or chronic dialysis
- Severe hepatic insufficiency such as with hepatic encephalopathy
- Malignancy or other non-cardiac condition limiting life expectancy to <3 years
- Require continuous home oxygen for severe pulmonary disease
- Current alcohol and/or drug abuse
- Participated in another interventional clinical study and treatment with another investigational product ≤30 days prior to randomization or plans to participate in any other trial/investigation during the duration of this study
- Mental or legal incapacitation and is unable to provide informed consent
- Immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is involved with this study
- Interstitial Lung Disease
- Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the course of the study
About this study
Official title: A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF) - VerICiguaT GlObal Study in Subjects With Heart Failure With Reduced EjectIon FrAction (VICTORIA)
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.
- Being tested
- Vericiguat, Placebo for vericiguat
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VericiguatDrug
Also called MK-1242
2.5, 5.0, or 10.0 mg orally once daily
Placebo for vericiguatDrug
2.5, 5.0, or 10.0 mg orally once daily
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo for vericiguat |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Time to First Occurrence of CV Death was analyzed using a one-sided stratified log-rank test. Randomized participants without a CV death 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 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.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Time to the First Occurrence of HF Hospitalization
Time to the First Occurrence of HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any HF hospitalization at the time of analysis were censored at their last available information, the date of their death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A 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.
Measured: 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)
Time to Total HF Hospitalizations (including first and recurring) was analyzed using an Andersen-Gill model. Randomized participants without any HF hospitalization at the time of analysis were censored at their last available information, the date of their death, or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A 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 of follow-up) is provided.
Measured: 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
Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization was analyzed using a one-sided stratified log-rank test. Randomized participants without any all-cause mortality event or HF hospitalization at the time of analysis were censored at their last available information or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A 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.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Time to All-Cause Mortality
Time to All-Cause Mortality was analyzed using a one-sided stratified log-rank test. Randomized participants without any all-cause mortality event at the time of analysis were censored at their last available information or the primary analysis database cutoff date of 18-June-2019, whichever occurred first. A 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.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Number of Participants Who Experienced One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Number of Participants Who Discontinued Treatment Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Percentage of Participants Who Experienced Symptomatic Hypotension
Study participants were monitored for symptomatic hypotension, an event of clinical interest, and results were reported.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Percentage of Participants Who Experienced Syncope
Study participants were monitored for syncope, an event of clinical interest, and results were reported.
Measured: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2016 (estimated)
- Study start20 Sep 2016
- Primary completion18 Jun 2019
- Study completion2 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 5,050 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bayer, Canadian VIGOUR Centre, Duke Clinical Research Institute
- Responsible party
- Sponsor
- Investigators
- Mahesh J. Patel, MD, Study director, Merck Sharp & Dohme LLCPaul W. Armstrong, MD, Study chair, Canadian VIGOUR Centre - University of AlbertaChristopher M. O'Connor, MD, Principal investigator, Inova Heart and Vascular InstituteBurkert Pieske, MD, Principal investigator, Charité University Medicine and German Heart Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02861534
- Sponsor's protocol ID
- 1242-001
- Other IDs
- 2016-000671-25, MK-1242-001, 2016
- Acronym
- VICTORIA
- Status last verified
- Nov 2021
- First submitted
- 5 Aug 2016
- Last updated
- 15 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: https://thecvc.ca/victoria/data-sharing/
Publications
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.
PubMed 31820546Shah 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. 2026 Feb;19(2):e013166. doi: 10.1161/CIRCHEARTFAILURE.125.013166. Epub 2025 Oct 8.
PubMed 41058565Khan 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.
PubMed 38934967Mentz 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.
PubMed 38363272Chew 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.
PubMed 37671551Lam 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.
PubMed 37565973Armstrong 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.
PubMed 37503602Ezekowitz 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.
PubMed 37417824Felker 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.
PubMed 37331690Butler 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.
PubMed 37137660Armstrong 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.
PubMed 36049817Senni 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.
PubMed 35880474Senni 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.
PubMed 35791083Butler 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.
PubMed 35656822Lam 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.
PubMed 34743540
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, Multi-Center Pivotal Phase III Clinical Outcome Trial of Efficacy and Safety of the Oral sGC Stimulator Vericiguat in Subjects With Heart Failure With Reduced Ejection Fraction (HFrEF) - VerICiguaT GlObal Study in Subjects With Heart Failure With Reduced EjectIon FrAction (VICTORIA)
- ClinicalTrials.gov ID
- NCT02861534
- Acronym / sponsor ID
- VICTORIA / 1242-001
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,050 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Collaborators
- Bayer, Canadian VIGOUR Centre, Duke Clinical Research Institute
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 18 Jun 2019 (actual)
- Study completion
- 2 Sep 2019 (actual)
- First posted
- 10 Aug 2016 (estimated)
- Results
- Posted 29 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vericiguat | Experimental | Drug: VericiguatParticipants 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. |
| Placebo | Placebo comparator | Drug: Placebo for vericiguatParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VericiguatAlso: MK-12422.5, 5.0, or 10.0 mg orally once daily | Drug | Vericiguat |
| Placebo for vericiguat2.5, 5.0, or 10.0 mg orally once daily | Drug | Placebo |
Primary outcome
Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
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.
9 secondary outcomes
Time to the First Occurrence of CV Death
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Time to the First Occurrence of HF Hospitalization
Time frame: 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)
Time frame: 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
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Time to All-Cause Mortality
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Number of Participants Who Experienced One or More Adverse Events
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Number of Participants Who Discontinued Treatment Due to an Adverse Event
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Percentage of Participants Who Experienced Symptomatic Hypotension
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Percentage of Participants Who Experienced Syncope
Time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31820546Pieske 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.
- Derived from this study: PubMed 41058565Shah 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. 2026 Feb;19(2):e013166. doi: 10.1161/CIRCHEARTFAILURE.125.013166. Epub 2025 Oct 8.
- Derived from this study: PubMed 38934967Khan 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.
- Derived from this study: PubMed 38363272Mentz 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.
- Derived from this study: PubMed 37671551Chew 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.
- Derived from this study: PubMed 37565973Lam 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.
- Derived from this study: PubMed 37503602Armstrong 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.
- Derived from this study: PubMed 37417824Ezekowitz 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.
- Derived from this study: PubMed 37331690Felker 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.
- Derived from this study: PubMed 37137660Butler 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.
- Derived from this study: PubMed 36049817Armstrong 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.
- Derived from this study: PubMed 35880474Senni 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.
- Individual participant dataSharing planned: Yes. https://thecvc.ca/victoria/data-sharing/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mahesh J. Patel, MD study director
Merck Sharp & Dohme LLC
Paul W. Armstrong, MD study chair
Canadian VIGOUR Centre - University of Alberta
Christopher M. O'Connor, MD principal investigator
Inova Heart and Vascular Institute
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vericiguat in people with Heart Failure and Chronic Heart Failure With Reduced Ejection Fraction, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization (time frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02861534, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2021.