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

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ClinicalTrials.gov Identifier: NCT02861534

Recruitment Status : Completed

First Posted : August 10, 2016

Results First Posted : June 29, 2020

Last Update Posted : November 15, 2021

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Sponsor:

Collaborators:

Bayer

Canadian VIGOUR Centre

Duke Clinical Research Institute

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Tracking Information

First Submitted Date ^ICMJE

August 5, 2016

First Posted Date ^ICMJE

August 10, 2016

Results First Submitted Date ^ICMJE

June 11, 2020

Results First Posted Date ^ICMJE

June 29, 2020

Last Update Posted Date

November 15, 2021

Actual Study Start Date ^ICMJE

September 20, 2016

Actual Primary Completion Date

June 18, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure Hospitalization [ Time Frame: Up to approximately 3.5 years ]

Change History

Current Secondary Outcome Measures ^ICMJE

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 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.
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 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.
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 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.
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 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.
Time to All-Cause Mortality [ Time Frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019) ]
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.
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) ]
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.
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) ]
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.
Percentage of Participants Who Experienced Symptomatic Hypotension [ Time Frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019) ]
Study participants were monitored for symptomatic hypotension, an event of clinical interest, and results were reported.
Percentage of Participants Who Experienced Syncope [ Time Frame: Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019) ]
Study participants were monitored for syncope, an event of clinical interest, and results were reported.

Original Secondary Outcome Measures ^ICMJE

Time to the First Occurrence of CV Death [ Time Frame: Up to approximately 3.5 years ]
Time to the First Occurrence of HF Hospitalization [ Time Frame: Up to approximately 3.5 years ]
Time to Total HF Hospitalizations (including frst and recurrent events) [ Time Frame: Up to approximately 3.5 years ]
Time to First Occurrence of Composite Endpoint of All-cause Mortality or HF Hospitalization [ Time Frame: Up to approximately 3.5 years ]
Time to All-cause Mortality [ Time Frame: Up to approximately 3.5 years ]

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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)

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.

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

Heart Failure
Chronic Heart Failure With Reduced Ejection Fraction

Intervention ^ICMJE

Drug: Vericiguat
2.5, 5.0, or 10.0 mg orally once daily

Other Name: MK-1242
Drug: Placebo for vericiguat
2.5, 5.0, or 10.0 mg orally once daily

Study Arms ^ICMJE

Experimental: Vericiguat
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.

Intervention: Drug: Vericiguat
Placebo Comparator: Placebo
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.

Intervention: Drug: Placebo for vericiguat

Publications *

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

5050

Original Estimated Enrollment ^ICMJE

4872

Actual Study Completion Date ^ICMJE

September 2, 2019

Actual Primary Completion Date

June 18, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Inclusion Criteria:

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.

Exclusion Criteria:

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
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

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

Not Provided

Removed Location Countries

Argentina, Australia, Austria, Belgium, Canada, Chile, China, Colombia, Czech Republic, Czechia, Denmark, Finland, France, Germany, Greece, Guatemala, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Norway, Peru, Philippines, Poland, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Administrative Information

NCT Number ^ICMJE

NCT02861534

Other Study ID Numbers ^ICMJE

1242-001
2016-000671-25 ( EudraCT Number )
MK-1242-001 ( Other Identifier: Merck Protocol Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	https://thecvc.ca/victoria/data-sharing/

Current Responsible Party

Merck Sharp & Dohme LLC

Original Responsible Party

Same as current

Current Study Sponsor ^ICMJE

Merck Sharp & Dohme LLC

Original Study Sponsor ^ICMJE

Same as current

Collaborators ^ICMJE

Bayer
Canadian VIGOUR Centre
Duke Clinical Research Institute

Investigators ^ICMJE

Study Director:	Mahesh J. Patel, MD	Merck Sharp & Dohme LLC
Study Chair:	Paul W. Armstrong, MD	Canadian VIGOUR Centre - University of Alberta
Principal Investigator:	Christopher M. O'Connor, MD	Inova Heart and Vascular Institute
Principal Investigator:	Burkert Pieske, MD	Charité University Medicine and German Heart Center

PRS Account

Merck Sharp & Dohme LLC

Verification Date

November 2021

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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