Clinical Trials List
Protocol NumberMK1242-001
NCT Number(ClinicalTrials.gov Identfier)NCT02861534
2016-10-26 - 2020-12-31
Phase III
Terminated6
ICD-10I50
Heart failure
A Randomized Parallel-Group, Placebo-Controlled, Double-Blind, Event-Driven, MultiCenter 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 Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme Corp.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Taipei Veterans General Hospital
Taiwan National PI
江晨恩
Co-Principal Investigator
- 林幸榮 Division of Family Medicine
- Kang-Ling Wang 醫學研究部
- Wen-Chung Yu Division of Cardiovascular Diseases
- Hao-min Cheng Division of General Internal Medicine
- Shih-Hsien Sung Division of Cardiovascular Diseases
- Tse-Min Lu Division of Family Medicine
The Actual Total Number of Participants Enrolled
20 Terminated
Audit
None
Co-Principal Investigator
- 李威廷 Division of General Internal Medicine
- Po-Sheng Chen Division of General Internal Medicine
- Ping-Yen Liu Division of Cardiovascular Diseases
- Po-Tseng Lee Division of Cardiovascular Diseases
- Cheng-Han Lee Division of Cardiovascular Diseases
- Ju-Yi Chen Division of Cardiovascular Diseases
- Yen-Wen Liu Division of Cardiovascular Diseases
- 李文煌 Division of Cardiovascular Diseases
- Chih-Hsin Hsu Division of General Internal Medicine
- Shih-Hung Chan Division of Cardiovascular Diseases
- 陳柏偉 Division of Cardiovascular Diseases
- 林志展 Division of Cardiovascular Diseases
- 黃成偉 Division of Cardiovascular Diseases
- Wei-Chuan Tsai Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 蔣俊彥 Division of Cardiovascular Diseases
- Zhih-Cherng Chen Division of Cardiovascular Diseases
- 洪俊聲 Division of Cardiovascular Diseases
- 施志遠 Division of Cardiovascular Diseases
- Wei-Ting Chang Division of Cardiovascular Diseases
- 周銘霆 Division of Cardiovascular Diseases
- Chia-Te Liao Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- CHO-KAI WU Division of Cardiovascular Diseases
- 張博淵 Division of Cardiovascular Diseases
- 林柏志 Division of Cardiovascular Diseases
- 洪啟盛 Division of Cardiovascular Diseases
- JEN-KUANG LEE Division of Cardiovascular Diseases
- LIAN-YU LIN Division of Cardiovascular Diseases
- YEN-HUNG LIN Division of Cardiovascular Diseases
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Heart Failure With Reduced Ejection Fraction (HFrEF)
Objectives
Primary Objective(s) & Hypothesis(es)
1) Objective: To evaluate the efficacy of the oral soluble guanylate cyclase (sGC)
stimulator MK-1242 (vericiguat) in comparison to placebo on a background of
standard of care in increasing the time to first occurrence of the composite of CV
death or HF hospitalization in subjects with HFrEF.
Hypothesis: MK-1242 is superior to placebo in increasing the time to first
occurrence of the composite of CV death or HF hospitalization in subjects with
HFrEF.
The study is considered to have met its primary objective if MK-1242 is superior to
placebo in the primary hypothesis testing at the final analysis, or the study is stopped
for overwhelming efficacy at the efficacy interim analysis.
Test Drug
MK-1242 (vericiguat)
Active Ingredient
vericiguat hydrochloride
Dosage Form
Tablet
Dosage
2.5/5/10 mg/Tablet
Endpoints
Primary Endpoint(s)
Time to the first occurrence of the composite endpoint of CV death or HF hospitalization.
Secondary Endpoints
Time to CV death
Time to first HF hospitalization
Time to total HF hospitalizations (first and recurrent)
Time to the composite of all-cause mortality or HF hospitalization
Time to all-cause mortality
Time to the first occurrence of the composite endpoint of CV death or HF hospitalization.
Secondary Endpoints
Time to CV death
Time to first HF hospitalization
Time to total HF hospitalizations (first and recurrent)
Time to the composite of all-cause mortality or HF hospitalization
Time to all-cause mortality
Inclution Criteria
Subject Inclusion Criteria
In order to be eligible for participation in this trial, the subject must:
1. Provide written informed consent for the trial. The subject may also provide consent
for Future Biomedical Research. However, the subject may participate in the main
trial without participating in Future Biomedical Research.
2. Be male or female, aged 18 years or older on the day of signing informed consent.
3. Have a history of chronic HF (NYHA class II-IV) on standard therapy before
qualifying HF decompensation.
4. Have a previous HF hospitalization within 6 months prior to randomization or IV
diuretic treatment for HF (without hospitalization) within 3 months prior to
randomization.
Note: No more than approximately 20% of subjects will be randomized with a
qualifying HF hospitalization >3 months prior to randomization.
5. Have brain natriuretic peptide (BNP) or NT-proBNP levels within 30 days prior to
randomization as follows:
NT-proBNP BNP
Sinus Rhythm ≥ 1000 pg/mL ≥ 300 pg/mL
Atrial Fibrillation ≥ 1600 pg/mL ≥ 500 pg/mL
Note: BNP cannot be used to determine eligibility for inclusion in subjects on
sacubitril/valsartan because sacubitril/valsartan led to ~15% increase in median
BNP in the PARADIGM-HF trial [9]. NT-proBNP must be used to confirm
eligibility for subjects taking sacubitril/valsartan.
6. Have a left ventricular ejection fraction (LVEF) of <45% assessed within 12 months
prior to randomization by any method (most recent measurement must be used to
determine eligibility).
7. Meet one of the following criteria:
a) The subject is a male.
b) The subject is a female who is not of reproductive potential, defined as a female
who either: (1) is postmenopausal (defined as at least 12 months with no menses in
women ≥45 years of age); (2) has had a hysterectomy and/or bilateral
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least
6 weeks prior to screening; OR (3) has a congenital or acquired condition that
prevents childbearing.
c) The subject is a female who is of reproductive potential and 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: (1) practice abstinence†
from heterosexual activity OR (2) use (or have her partner use) acceptable
contraception during heterosexual activity. Acceptable methods of contraception
are‡
:
Single method (one of the following is acceptable):
• Intrauterine device (IUD)
• Vasectomy of a female subject’s male partner
• Contraceptive rod implanted into the skin
Combination method (requires use of two of the following):
• Diaphragm with spermicide (cannot be used in conjunction with cervical
cap/spermicide)
• Cervical cap with spermicide (nulliparous women only)
• Contraceptive sponge (nulliparous women only)
• Male condom or female condom (cannot be used together)
• Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or
subcutaneous contraceptive injection.
†Abstinence (relative to heterosexual activity) can be used as the sole method of
contraception if it is consistently employed as the subject’s preferred and usual
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation
methods, etc.) and withdrawal are not acceptable methods of contraception.
‡
If a contraceptive method listed above is restricted by local regulations/guidelines,
then it does not qualify as an acceptable method of contraception for subjects
participating at sites in this country/region.
In order to be eligible for participation in this trial, the subject must:
1. Provide written informed consent for the trial. The subject may also provide consent
for Future Biomedical Research. However, the subject may participate in the main
trial without participating in Future Biomedical Research.
2. Be male or female, aged 18 years or older on the day of signing informed consent.
3. Have a history of chronic HF (NYHA class II-IV) on standard therapy before
qualifying HF decompensation.
4. Have a previous HF hospitalization within 6 months prior to randomization or IV
diuretic treatment for HF (without hospitalization) within 3 months prior to
randomization.
Note: No more than approximately 20% of subjects will be randomized with a
qualifying HF hospitalization >3 months prior to randomization.
5. Have brain natriuretic peptide (BNP) or NT-proBNP levels within 30 days prior to
randomization as follows:
NT-proBNP BNP
Sinus Rhythm ≥ 1000 pg/mL ≥ 300 pg/mL
Atrial Fibrillation ≥ 1600 pg/mL ≥ 500 pg/mL
Note: BNP cannot be used to determine eligibility for inclusion in subjects on
sacubitril/valsartan because sacubitril/valsartan led to ~15% increase in median
BNP in the PARADIGM-HF trial [9]. NT-proBNP must be used to confirm
eligibility for subjects taking sacubitril/valsartan.
6. Have a left ventricular ejection fraction (LVEF) of <45% assessed within 12 months
prior to randomization by any method (most recent measurement must be used to
determine eligibility).
7. Meet one of the following criteria:
a) The subject is a male.
b) The subject is a female who is not of reproductive potential, defined as a female
who either: (1) is postmenopausal (defined as at least 12 months with no menses in
women ≥45 years of age); (2) has had a hysterectomy and/or bilateral
oophorectomy, bilateral salpingectomy, or bilateral tubal ligation/occlusion at least
6 weeks prior to screening; OR (3) has a congenital or acquired condition that
prevents childbearing.
c) The subject is a female who is of reproductive potential and 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: (1) practice abstinence†
from heterosexual activity OR (2) use (or have her partner use) acceptable
contraception during heterosexual activity. Acceptable methods of contraception
are‡
:
Single method (one of the following is acceptable):
• Intrauterine device (IUD)
• Vasectomy of a female subject’s male partner
• Contraceptive rod implanted into the skin
Combination method (requires use of two of the following):
• Diaphragm with spermicide (cannot be used in conjunction with cervical
cap/spermicide)
• Cervical cap with spermicide (nulliparous women only)
• Contraceptive sponge (nulliparous women only)
• Male condom or female condom (cannot be used together)
• Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or
subcutaneous contraceptive injection.
†Abstinence (relative to heterosexual activity) can be used as the sole method of
contraception if it is consistently employed as the subject’s preferred and usual
lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs.
Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation
methods, etc.) and withdrawal are not acceptable methods of contraception.
‡
If a contraceptive method listed above is restricted by local regulations/guidelines,
then it does not qualify as an acceptable method of contraception for subjects
participating at sites in this country/region.
Exclusion Criteria
Subject Exclusion Criteria
The subject must be excluded from participating in the trial if the subject:
1. Is clinically unstable at the time of randomization as defined by:
a. Administration of any intravenous treatment within 24 hours prior to
randomization, and/or
b. Systolic blood pressure (SBP) <100 mmHg or symptomatic hypotension.
2. Has concurrent or anticipated use of long-acting nitrates or NO donors including
isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil
or transdermal nitroglycerin (NTG) patch, and molsidomine.
Note: Co-administration of short-acting nitrates, i.e., sublingual nitroglycerin spray
as indicated for angina attacks, is allowed (See section 5.5.2).
3. Has concurrent use or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors
such as vardenafil, tadalafil, and sildenafil.
4. Has concurrent use or anticipated use of a sGC stimulator such as riociguat.
5. Has known allergy or sensitivity to any sGC stimulator.
6. Is 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.
Cardiac Comorbidity
7. Has primary valvular heart disease requiring surgery or intervention, or is within
3 months after valvular surgery or intervention.
8. Has hypertrophic obstructive cardiomyopathy.
9. Has acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy.
10. Has post-heart transplant cardiomyopathy.
11. Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
12. Has 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 prior to randomization, or indication for
coronary revascularization at time of randomization.
13. Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within
60 days prior to randomization.
14. Has complex congenital heart disease.
15. Has active endocarditis or constrictive pericarditis.
Non-cardiac comorbidity
16. Has an estimated glomerular filtration rate (eGFR) calculated based on the
Modification of Diet in Renal Disease (MDRD) equation <15 mL/min/1.73 m2
or
chronic dialysis.
Note: No more than approximately 15% of subjects will enroll with an eGFR in the
15 mL/min/1.73 m2
to 30 mL/min/1.73 m2
range.
17. Has severe hepatic insufficiency such as with hepatic encephalopathy.
18. Has malignancy or other non-cardiac condition limiting life expectancy to <3 years.
19. Requires continuous home oxygen for severe pulmonary disease.
20. Has current alcohol and/or drug abuse.
21. Has 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.
22. Has a mental or legal incapacitation and is unable to provide informed consent.
23. Has a medical disorder, condition, or history thereof that in the opinion of the
investigator would impair the subject’s ability to participate or complete the study.
24. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling
or child) who is investigational site or sponsor staff directly involved with this trial.
25. Has Interstitial Lung Disease.
26. Is breastfeeding or plans to breastfeed during the course of the trial.
The subject must be excluded from participating in the trial if the subject:
1. Is clinically unstable at the time of randomization as defined by:
a. Administration of any intravenous treatment within 24 hours prior to
randomization, and/or
b. Systolic blood pressure (SBP) <100 mmHg or symptomatic hypotension.
2. Has concurrent or anticipated use of long-acting nitrates or NO donors including
isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil
or transdermal nitroglycerin (NTG) patch, and molsidomine.
Note: Co-administration of short-acting nitrates, i.e., sublingual nitroglycerin spray
as indicated for angina attacks, is allowed (See section 5.5.2).
3. Has concurrent use or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors
such as vardenafil, tadalafil, and sildenafil.
4. Has concurrent use or anticipated use of a sGC stimulator such as riociguat.
5. Has known allergy or sensitivity to any sGC stimulator.
6. Is 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.
Cardiac Comorbidity
7. Has primary valvular heart disease requiring surgery or intervention, or is within
3 months after valvular surgery or intervention.
8. Has hypertrophic obstructive cardiomyopathy.
9. Has acute myocarditis, amyloidosis, sarcoidosis, Takotsubo cardiomyopathy.
10. Has post-heart transplant cardiomyopathy.
11. Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia.
12. Has 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 prior to randomization, or indication for
coronary revascularization at time of randomization.
13. Has symptomatic carotid stenosis, transient ischemic attack (TIA) or stroke within
60 days prior to randomization.
14. Has complex congenital heart disease.
15. Has active endocarditis or constrictive pericarditis.
Non-cardiac comorbidity
16. Has an estimated glomerular filtration rate (eGFR) calculated based on the
Modification of Diet in Renal Disease (MDRD) equation <15 mL/min/1.73 m2
or
chronic dialysis.
Note: No more than approximately 15% of subjects will enroll with an eGFR in the
15 mL/min/1.73 m2
to 30 mL/min/1.73 m2
range.
17. Has severe hepatic insufficiency such as with hepatic encephalopathy.
18. Has malignancy or other non-cardiac condition limiting life expectancy to <3 years.
19. Requires continuous home oxygen for severe pulmonary disease.
20. Has current alcohol and/or drug abuse.
21. Has 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.
22. Has a mental or legal incapacitation and is unable to provide informed consent.
23. Has a medical disorder, condition, or history thereof that in the opinion of the
investigator would impair the subject’s ability to participate or complete the study.
24. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling
or child) who is investigational site or sponsor staff directly involved with this trial.
25. Has Interstitial Lung Disease.
26. Is breastfeeding or plans to breastfeed during the course of the trial.
The Estimated Number of Participants
-
Taiwan
90 participants
-
Global
4872 participants
