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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02861534
Recruitment Status : Completed
First Posted : August 10, 2016
Results First Posted : June 29, 2020
Last Update Posted : July 14, 2020
Sponsor:
Collaborators:
Bayer
Canadian VIGOUR Centre
Duke Clinical Research Institute
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 July 14, 2020
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
 (submitted: June 11, 2020)
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
 (submitted: August 5, 2016)
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
 (submitted: June 11, 2020)
  • 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
 (submitted: August 5, 2016)
  • 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
 (submitted: July 4, 2019)
5050
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2016)
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 No
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/publications/data-sharing/victoria/
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE
  • Bayer
  • Canadian VIGOUR Centre
  • Duke Clinical Research Institute
Investigators  ICMJE
Study Director: Mahesh J. Patel, MD Merck Sharp & Dohme Corp.
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 Corp.
Verification Date July 2020

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