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

November 12, 2021 updated by: Merck Sharp & Dohme LLC

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

5050

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Vericiguat
2.5, 5.0, or 10.0 mg orally once daily
Other Names:
  • MK-1242
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.
Drug: Placebo for vericiguat
2.5, 5.0, or 10.0 mg orally once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 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.
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 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.
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 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.
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)
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.
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)
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.
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)
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.
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)
Study participants were monitored for symptomatic hypotension, an event of clinical interest, and results were reported.
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)
Study participants were monitored for syncope, an event of clinical interest, and results were reported.
Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Bayer
Duke Clinical Research Institute
Canadian VIGOUR Centre

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 20, 2016

Primary Completion (Actual)

June 18, 2019

Study Completion (Actual)

September 2, 2019

Study Registration Dates

First Submitted

August 5, 2016

First Submitted That Met QC Criteria

August 5, 2016

First Posted (Estimate)

August 10, 2016

Study Record Updates

Last Update Posted (Actual)

November 15, 2021

Last Update Submitted That Met QC Criteria

November 12, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

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

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

https://thecvc.ca/victoria/data-sharing/

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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