Study 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

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 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.
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

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

Where to participate

Status	Institution	Location
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.
Time 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.
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 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 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.
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 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 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.
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
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.
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
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.
Time 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.
Time 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.
Time 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