NCT02861534: VICTORIA

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

Completed Phase 3 Results posted Last updated 15 November 2021

What this trial tests

Phase 3 trial testing Vericiguat in Heart Failure in 5,050 participants. Completed in 2 September 2019.

Timeline

20 September 2016

Primary endpoint
18 June 2019

2 September 2019

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	5,050
Start date	20 September 2016
Primary completion	18 June 2019
Estimated completion	2 September 2019

Drugs / interventions tested

• Vericiguat (VERICIGUAT) — full drug profile →
• Placebo for vericiguat — full drug profile →

Conditions studied

• Heart Failure — all drugs for Heart Failure →
• Chronic Heart Failure With Reduced Ejection Fraction — all drugs for Chronic Heart Failure With Reduced Ejection Fraction →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Heart Failure or Chronic Heart Failure With Reduced Ejection Fraction. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to the First Occurrence of CV Death Secondary · 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.

Group	Value	95% CI
Vericiguat	12.9
Placebo	13.9

Time to the First Occurrence of HF Hospitalization Secondary · 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.

Group	Value	95% CI
Vericiguat	25.9
Placebo	29.1

Time to First Occurrence of Composite Endpoint of Cardiovascular (CV) Death or Heart Failure (HF) Hospitalization Primary · 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 (nu

Group	Value	95% CI
Vericiguat	33.6	41.5 – 46.4
Placebo	37.8	44.4 – 49.4

Time to Total HF Hospitalizations (Including First and Recurrent Events) Secondary · 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 prov

Group	Value	95% CI
Vericiguat	38.3
Placebo	42.4

Time to First Occurrence of Composite Endpoint of All-Cause Mortality or HF Hospitalization Secondary · 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

Group	Value	95% CI
Vericiguat	35.9
Placebo	40.1

Time to All-Cause Mortality Secondary · 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.

Group	Value	95% CI
Vericiguat	16.0
Placebo	16.9

Number of Participants Who Experienced One or More Adverse Events Secondary · 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.

Group	Value	95% CI
Vericiguat	2027
Placebo	2036

Number of Participants Who Discontinued Treatment Due to an Adverse Event Secondary · 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.

Group	Value	95% CI
Vericiguat	167
Placebo	158

Percentage of Participants Who Experienced Symptomatic Hypotension Secondary · 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.

Group	Value	95% CI
Vericiguat	9.1
Placebo	7.9

Percentage of Participants Who Experienced Syncope Secondary · 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.

Group	Value	95% CI
Vericiguat	4.0
Placebo	3.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 35 months (through Last Subject Last Visit date of 02-Sept-2019). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vericiguat

Serious: 852/2519 (34%)

Deaths: 553/2526

Placebo

Serious: 897/2515 (36%)

Deaths: 561/2524

Serious adverse events (783 terms)

Reaction	System	Vericiguat	Placebo
Cardiac failure	Cardiac disorders	—	—
Pneumonia	Infections and infestations	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Hypotension	Vascular disorders	—	—
Syncope	Nervous system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Chronic kidney disease	Renal and urinary disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Renal failure	Renal and urinary disorders	—	—
Atrial fibrillation	Cardiac disorders	—	—
Ventricular tachycardia	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Septic shock	Infections and infestations	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Gout	Metabolism and nutrition disorders	—	—
Hypoglycaemia	Metabolism and nutrition disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Vericiguat	Placebo
Hypotension	Vascular disorders	—	—
Dizziness	Nervous system disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Cardiac failure	Cardiac disorders	—	—
Hyperkalaemia	Metabolism and nutrition disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Diarrhoea	Gastrointestinal disorders	—	—

Most-reported serious reactions: Cardiac failure, Pneumonia, Acute kidney injury, Hypotension, Syncope, Anaemia, Chronic kidney disease, Chronic obstructive pulmonary disease.

Data from ClinicalTrials.gov NCT02861534 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Vericiguat in Patients with Heart Failure and Reduced Ejection Fraction.
   Armstrong PW, Pieske B, Anstrom KJ, Ezekowitz J, et al · · 2020 · cited 738× · PMID 32222134 · DOI 10.1056/nejmoa1915928
2. Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
   Tejero J, Shiva S, Gladwin MT. · · 2019 · cited 357× · PMID 30379623 · DOI 10.1152/physrev.00036.2017
3. Targeting mitochondrial dysfunction and oxidative stress in heart failure: Challenges and opportunities.
   Kiyuna LA, Albuquerque RPE, Chen CH, Mochly-Rosen D, et al · · 2018 · cited 160× · PMID 30227272 · DOI 10.1016/j.freeradbiomed.2018.09.019
4. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of the Oral Soluble Guanylate Cyclase Stimulator: The VICTORIA Trial.
   Armstrong PW, Roessig L, Patel MJ, Anstrom KJ, et al · · 2018 · cited 139× · PMID 29032136 · DOI 10.1016/j.jchf.2017.08.013
5. cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.
   Friebe A, Sandner P, Schmidtko A. · · 2020 · cited 102× · PMID 31853617 · DOI 10.1007/s00210-019-01779-z
6. N-Terminal Pro-B-Type Natriuretic Peptide and Clinical Outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction Study.
   Ezekowitz JA, O'Connor CM, Troughton RW, Alemayehu WG, et al · · 2020 · cited 97× · PMID 33039447 · DOI 10.1016/j.jchf.2020.08.008
7. Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial.
   Voors AA, Mulder H, Reyes E, Cowie MR, et al · · 2021 · cited 73× · PMID 33999486 · DOI 10.1002/ejhf.2221
8. Clinical Outcomes and Response to Vericiguat According to Index Heart Failure Event: Insights From the VICTORIA Trial.
   Lam CSP, Giczewska A, Sliwa K, Edelmann F, et al · · 2021 · cited 64× · PMID 33185650 · DOI 10.1001/jamacardio.2020.6455