I50 NULL NULL
Conditions
Interventions
Masked Vericiguat tablet starting with 2.5 mg per day by mouth, increasing on day 14 to 5mg per day and on day 28 at 10mg per day until week 24. This last dose will continue to be delivered until the
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Is male or female, at least 18 years of age, at the time of providing documented informed consent. Has a history of chronic HF (NYHA Class II to IV) on GDMT with no events of HFH within 6 months or outpatient IV diuretic use within 3 months before randomization. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. The participant may also provide consent/assent for FBR. However, the participant may participate in the study without participating in FBR. Has a screening NT-proBNP level within 30 days before randomization. For participants with multiple NT-proBNP results during screening, the most recent value will be used to determine eligibility at the Randomization Visit. Has an LVEF of =40% assessed within 12 months before randomization by any imaging method. The most recent measurement must be used to determine eligibility. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a WOCBP or Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 1 month after the last dose of study intervention.
Exclusion criteria
Exclusion criteria: Had any discontinuation or dose modification of GDMT (including beta blockers, ACEI/ARBs, ARNI, MRAs, hydralazine-nitrate combinations, SGLT2is, or ivabradine) or vericiguat within 4 weeks before randomization. Has concurrent or anticipated concomitant use of PDE5 inhibitors such as vardenafil, tadalafil, and sildenafil during the study. Has concurrent use of an sGC stimulator such as riociguat or vericiguat. Has participated in another interventional clinical study or has been treated with another investigational product =30 days before randomization or plans to participate in any other study or study intervention during this study. Has a recent history (within the last year) of drug or alcohol abuse or dependence. Is pregnant or breastfeeding or plans to become pregnant or to breastfeed during the study. Has a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the participant’s ability to participate in or complete the study. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study. Has hypertrophic cardiomyopathy. Has received a heart transplan Has tachycardia-induced cardiomyopathy and/or uncontrolled tachyarrhythmia. Has symptomatic carotid stenosis, TIA, or stroke within 3 months before randomization. Has acute coronary syndrome (unstable angina, NSTEMI, or STEMI), undergone CABG or PCI within 3 months before randomization, or indication for coronary revascularization at the time of randomization. Has a history of repaired or unrepaired simple congenital heart disease (eg, atrial or ventricular septal defects, or patent ductus arteriosus) with ongoing hemodynamically significant residual lesions, or any history of complex congenital heart disease (eg, tetralogy of Fallot, transposition of the great arteries, single ventricle disease) regardless of repair status. Has malignancy or other noncardiac condition limiting life expectancy to <3 years. Requires continuous home oxygen for severe pulmonary disease. Has interstitial lung disease. Has amyloidosis or sarcoidosis. Has SBP <100 mm Hg or symptomatic hypotension. Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other sGC stimulator. Is awaiting heart transplantation (United Network for Organ Sharing Class 1A / 1B or equivalent), is receiving continuous IV infusion of an inotrope, or has or anticipates receiving an implanted ventricular assist device. Has active endocarditis or constrictive pericarditis. Has an eGFR based on the CKD-EPI Creatinine Equation of <15 mL/min/1.73 m2 within 30 days before randomization or is on chronic dialysis. For participants with multiple eGFR results during screening, the most recent value will be used to determine eligibility at the Randomization Visit. Has primary valvular heart disease requiring surgical procedure or intervention or has undergone a vascular surgical procedure or intervention within 3 months before randomization. Has acute myocarditis or Takotsubo cardiomyopathy. Has severe hepatic insufficiency such as with hepatic encephalopathy, hepatic laboratory abnormalities (ALT or AST =3 × ULN or total bilirubin =2 × ULN) or ALBI Grade 3. Screening albumin, ALT, AST, and total bilirubin results within 30 days before randomization may be used for assessment of laboratory abnormalities or the calculation of the ALBI score. For participants with mul
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to first event of CV death or HFH PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first CV death event or HFH. | — |
Secondary
| Measure | Time frame |
|---|---|
| Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to first event of CV death or HFH PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first CV death event or HFH. ;Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to CV death PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to CV death ;Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to the first event of HFH PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first HFH event ;Andersen-Gill model NAME OF THE RESULT: Time from randomization to total HFH events (including the first and recurrent events) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to all HFH events (first and recurring) ;Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to first event of all-cause mortality or HFH PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first event of all-cause mortality or HFH ;Kaplan Meier Method/Stratified Log-Rank Test/ Cox proportional hazards model stratified using the stratification factor for randomization NAME OF THE RESULT: Time from randomization to all-cause mortality PERIOD OF TIME WHERE TE MEASUREMENT WI | — |
Countries
Australia, Brazil, Canada, Chile, China, Colombia, Hong Kong, Israel, Korea South, Malasya, Mexico, New Zealand, Peru, Puerto Rico, Russian Federation, Singapore, South Africa, Taiwan, Turkey, Ukraine, United States
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed