check_circleStudy Completed

Heart failure, Chronic heart failure with reduced ejection fraction

Bayer Identifier:

16493

ClinicalTrials.gov Identifier:

NCT02861534

EudraCT Number:

2016-000671-25

EU CT Number:

Not Available
A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction (HFrEF) (MK-1242-001) (VICTORIA)

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

18 - N/A
  • - 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 Nterminal
    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.

  • - 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

Trial summary

Enrollment Goal
5050
Trial Dates
September 2016 - September 2019
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Verquvo (Vericiguat, BAY1021189)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Sapporo, 060-0004, Japan
Completed
Morioka, 020-0066, Japan
Completed
Sendai, 983-8512, Japan
Completed
Funabashi, 273-8588, Japan
Completed
Itabashi-ku, 173-8610, Japan
Completed
Meguro-ku, 153-0051, Japan
Completed
Ota-ku, 143-8541, Japan
Completed
Yokohama, 227-8501, Japan
Completed
Fukui, 910-8526, Japan
Completed
Shizuoka, 420-8527, Japan
Completed
Nagoya, 464-8547, Japan
Completed
Nagoya, 457-8510, Japan
Completed
Kyoto, 601-1495, Japan
Completed
Osaka, 530-0001, Japan
Completed
Hirakata, 573-0153, Japan
Completed
Suita, 565-0862, Japan
Completed
Matsue, 690-8509, Japan
Completed
Okayama, 700-8557, Japan
Withdrawn
Hatsukaichi, 738-8503, Japan
Completed
Kanonji, 769-1695, Japan
Completed
Kitakyushu, 800-0296, Japan
Completed
Nagasaki, 852-8501, Japan
Completed
Miyazaki, 880-2102, Japan
Completed
Sayama, 350-1305, Japan
Completed
Sayama, 350-1305, Japan
Completed
Sagamihara, 252-5188, Japan
Completed
Uji, 611-0041, Japan
Completed
Osaka, 543-0035, Japan
Withdrawn
Wakayama, 640-8505, Japan
Completed
Naha, 902-8511, Japan
Completed
Wako, 351-0102, Japan
Completed
Bunkyo-ku, 113-8431, Japan
Completed
Bunkyo-ku, 113-8655, Japan
Completed
Yokohama, 222-0036, Japan
Completed
Suita, 564-8565, Japan
Withdrawn
Osaka, 530-8480, Japan
Completed
Kishiwada, 596-0042, Japan
Completed
Takarazuka, 665-0873, Japan
Completed
Hamada, 697-8511, Japan
Completed
Kitakyushu, 805-8508, Japan
Withdrawn
Kitakyushu, 802-8517, Japan
Withdrawn
Kagoshima, 892-0822, Japan
Completed
Kagoshima, 892-0822, Japan
Completed
Meguro-ku, 152-8902, Japan
Completed
Koga, 306-0041, Japan
Completed
Adachi-ku, 123-0845, Japan
Completed
Shibuya-ku, 150-0013, Japan
Completed
Shinjuku-ku, 160-0023, Japan
Completed
Hachioji, 192-0918, Japan
Completed
Shinagawa-ku, 141-0001, Japan
Completed
Kawasaki, 211-8510, Japan
Completed
Yokohama, 247-8581, Japan
Completed
Toyama, 930-8550, Japan
Completed
Toyama, 930-0194, Japan
Completed
Kanazawa, 920-8530, Japan
Withdrawn
Fukui, 918-8503, Japan
Completed
Nagoya, 454-8502, Japan
Withdrawn
Nagoya, 453-8511, Japan
Completed
Nagoya, 460-0001, Japan
Completed
Kyoto, 602-8026, Japan
Completed
Osaka, 558-8558, Japan
Completed
Higashiosaka, 578-8588, Japan
Completed
Suita, 565-0871, Japan
Completed
Kobe, 650-0047, Japan
Completed
Takarazuka, 665-0022, Japan
Withdrawn
Onomichi, 722-8508, Japan
Completed
Kurume, 830-8543, Japan
Withdrawn
Kumamoto, 860-0008, Japan
Completed
Shimotsuke, 329-0498, Japan
Completed
Kawasaki, 211-8533, Japan
Completed
Yokohama, 232-0024, Japan
Withdrawn
Toyoake, 470-1192, Japan
Completed
Kyoto, 602-8566, Japan
Completed
Kobe, 654-0026, Japan
Withdrawn
Kakegawa, 436-8555, Japan
Completed
Fukuoka, 812-8582, Japan
Completed
Funabashi, 274-8503, Japan
Completed
Matsudo, 270-2251, Japan
Completed
Takatsuki, 569-1096, Japan
Completed
Kobe, 655-0017, Japan
Completed
Matsuyama, 790-0062, Japan
Completed
Nahariya, 2210001, Israel
Completed
Frankfurt, 60596, Germany
Completed
Boston, 02114-2696, United States
Completed
Sagamihara, 252-0375, Japan
Completed
Longueuil, J4N 1E1, Canada
Completed
Graz, 8036, Austria
Completed
St. Petersburg, 194354, Russian Federation
Completed
Chesterfield, S44 5DX, United Kingdom
Completed
San Juan, 00921, Puerto Rico
Completed
PARIS cedex 10, 75475, France
Completed
Wroclaw, 50-981, Poland
Completed
Bergamo, 24127, Italy
Completed
El Palmar (Murcia), 30120, Spain
Completed
BRUXELLES - BRUSSEL, 1200, Belgium
Completed
SNEEK, 8601 ZK, Netherlands
Completed
Malmö, 205 02, Sweden
Completed
Svendborg, DK-5700, Denmark
Completed
Oslo, 0424, Norway
Completed
Praha 4, 140 21, Czechia
Completed
Kistarcsa, 2143, Hungary
Completed
Istanbul, 34304, Turkey
Completed
Alexandroupoli, 68100, Greece
Completed
Seoul, 02841, Korea, Republic Of
Completed
Lausanne, 1011, Switzerland
Completed
Espoo, 02740, Finland
Completed
Taipei, 11217, Taiwan
Completed
Sarawak, 93400, Malaysia
Completed
Singapore, 119074, Singapore
Completed
Christchurch, 8140, New Zealand
Completed
Dublin, DUBLIN 4, Ireland
Completed
Querétaro, 76000, Mexico
Completed
Johannesburg, 2157, South Africa
Completed
Murdoch, 6150, Australia
Completed
Mar del Plata, B7600FZN, Argentina
Completed
Chile
Completed
Colombia
Withdrawn
Brazil
Completed
Hong Kong, Hong Kong
Completed
Manila, 1000, Philippines
Completed
Kashihara, 634-8522, Japan
Completed
Aki-gun, 735-8585, Japan
Completed
Kobe, 654-0155, Japan
Completed
Tachikawa, 190-0014, Japan
Completed
Niigata, 950-2087, Japan
Completed
Higashiibaraki, 311-3193, Japan
Completed
Kanazawa, 920-8650, Japan
Completed
Iwakuni, 740-8510, Japan
Completed
Shinjuku-ku, 162-8666, Japan
Completed
Nakagami-gun, 901-2393, Japan
Withdrawn
Sapporo, 060-0031, Japan
Withdrawn
Sapporo, 060-0031, Japan
Completed
Koshigaya, 343-8555, Japan
Completed
Nagano, 388-8004, Japan
Completed
Nagasaki, 850-8555, Japan
Completed
Oita, 870-0192, Japan
Completed
Shobara, 727-0013, Japan
Completed
Yonago, 683-8605, Japan
Completed
Nagaoka, 940-8621, Japan
Completed
China
Completed
Ukraine
Completed
Peru
Completed
Guatemala

Primary Outcome

  • 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.
    date_rangeTime Frame:
    Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Secondary Outcome

  • 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.
    date_rangeTime 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 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.
    date_rangeTime 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 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.
    date_rangeTime 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 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.
    date_rangeTime Frame:
    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.
    date_rangeTime 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
    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.
    date_rangeTime 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
    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.
    date_rangeTime Frame:
    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.
    date_rangeTime Frame:
    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.
    date_rangeTime Frame:
    Up to approximately 33 months (through primary analysis database cutoff date of 18-June-2019)

Trial design

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)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
2