Heart Failure With Reduced Ejection Fraction (HFrEF)Phase 4VERICIGUATNCT07697833
Comparing the Efficacy and Safety of Vericiguat With Standard Medical Treatment in Heart Failure Patients
A Phase 4 study testing Vericiguat tablet in people with Heart Failure With Reduced Ejection Fraction (HFrEF), run by National Institute of Cardiovascular Diseases, Pakistan.
Trial summary
To compare the effectiveness and safety of Vericiguat with Standard Medical Treatment in Patients with Heart Failure and Reduced Ejection Fraction Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction (HFrEF)
- What is being tested?
- Vericiguat tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 500 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2026to 31 Jul 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >18 years of any gender
- Chronic heart failure (New York Heart Association [NYHA] functional class II, III, or IV), a reduced left ventricular ejection fraction of less than 45% within 12 months before randomization
- Elevated natriuretic peptide level: (For patients in sinus rhythm, the criteria include a plasma B-type natriuretic peptide (BNP) level of at least 300 pg per milliliter or an NT-proBNP level of at least 1000 pg per milliliter. For patients in atrial fibrillation, the criteria included a BNP level of at least 500 pg per milliliter or an NT-proBNP level of at least 1600 pg per milliliter).
- Evidence of worsening heart failure.
- The percentage of enrolled patients with an estimated glomerular filtration rate of 15 to 30 ml per minute per 1.73 m2 of body-surface area was capped at 15%.
- Patients on guideline-based medical therapy 3 months
- Written and informed consent.
Who cannot join
- Systolic blood pressure of less than 100 mm Hg.
- Concurrent or anticipated use of long-acting nitrates.
- Use of intravenous inotropes or implantable left ventricular assist devices.
- Not on standard of care medical treatment for heart failure.
- Unwillingness to give consent
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Comparing the Efficacy and Safety of Vericiguat With Standard Medical Treatment in Patients With Heart Failure and Reduced Ejection Fraction: Randomized, Placebo-controlled, Parallel-group, Double-blind Trial
To compare the effectiveness and safety of Vericiguat with Standard Medical Treatment in Patients with Heart Failure and Reduced Ejection Fraction
Read the detailed description
Heart failure with reduced ejection fraction (HFrEF) remains a major cause of morbidity, mortality, and healthcare utilization despite advances in guideline-directed medical therapy. Patients who experience worsening heart failure events, including hospitalization or the need for urgent outpatient treatment, remain at increased risk of recurrent cardiovascular events and represent a high-risk population requiring additional therapeutic strategies.
The nitric oxide-soluble guanylate cyclase (NO-sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in maintaining cardiovascular function. In heart failure, endothelial dysfunction and reduced nitric oxide bioavailability may impair this pathway, contributing to vascular dysfunction, myocardial remodeling, and disease progression.
Vericiguat is an oral soluble guanylate cyclase stimulator that enhances cGMP production by directly stimulating soluble guanylate cyclase and increasing its sensitivity to endogenous nitric oxide. This mechanism provides a novel therapeutic approach that differs from conventional heart failure treatments targeting neurohormonal pathways.
Previous clinical evidence, including the VICTORIA trial, demonstrated that vericiguat reduced the risk of cardiovascular death or first hospitalization for heart failure among patients with chronic heart failure and recent worsening heart failure events. However, further evaluation of its effectiveness and safety in specific clinical settings and populations remains important.
This randomized, placebo-controlled, double-blind clinical trial will evaluate the effectiveness and safety of vericiguat in patients with heart failure with reduced ejection fraction receiving standard medical therapy. The study aims to determine whether the addition of vericiguat provides further clinical benefit compared with standard therapy alone in this high-risk patient population.
- Being tested
- Vericiguat tablet, Placebo
- Keywords
- Vericiguat, Heart Failure, Reduced Ejection Fraction (HFrEF), Chronic Heart Failure, Cardiovascular Diseases, Randomized Controlled Trial, Double Blind, Placebo-Controlled, Soluble Guanylate Cyclase Stimulator, NT-proBNP
- Medical subject headings
- Heart Failure, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vericiguat tabletDrug
Also called VERIZOT
Vericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care
PlaceboDrug
Also called VERIZOT
Participants will receive a matching placebo tablet. The placebo will follow the same dosing schedule as the study drug (2.5 mg, 5 mg, and 10 mg) to maintain blinding.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Vericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care Receives: Drug: Vericiguat tablet |
| Placebo | Placebo comparator | Standard of care medications with placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated, patient-reported instrument that assesses health status, including symptoms, physical limitations, social limitations, and quality of life in patients with heart failure. The Overall Summary Score ranges from 0 to 100, with higher scores indicating better health status. The primary endpoint is the change in the KCCQ-12 Overall Summary Score from baseline to Month 6.
Measured: Baseline to Month 6
Secondary outcomes (1)
First Hospitalization for Heart Failure
Time to first hospitalization for worsening heart failure during the study follow-up.
Measured: From enrollment to Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2026
- Study start15 Jul 2026 (estimated)
- Primary completion15 May 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Cardiovascular Diseases, Pakistan
- Sponsor type
- University, hospital or other
- Collaborators
- Horizon Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Ghazala Irfan, FCPS, Principal investigator, National Institute of Cardiovascular Diseases Karachi, Pakistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07697833
- Sponsor's protocol ID
- IRB-17/2026
- Acronym
- VERICIGUAT
- Status last verified
- Jul 2026
- First submitted
- 30 Jun 2026
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing the Efficacy and Safety of Vericiguat With Standard Medical Treatment in Patients With Heart Failure and Reduced Ejection Fraction: Randomized, Placebo-controlled, Parallel-group, Double-blind Trial
- ClinicalTrials.gov ID
- NCT07697833
- Acronym / sponsor ID
- VERICIGUAT / IRB-17/2026
- Keywords
- Vericiguat, Heart Failure, Reduced Ejection Fraction (HFrEF), Chronic Heart Failure, Cardiovascular Diseases, Randomized Controlled Trial, Double Blind, Placebo-Controlled
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- National Institute of Cardiovascular Diseases, PakistanUniversity, hospital or other
- Collaborators
- Horizon Pharmaceuticals
- Study start
- 15 Jul 2026 (estimated)
- Primary completion
- 15 May 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 13 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare the effectiveness and safety of Vericiguat with Standard Medical Treatment in Patients with Heart Failure and Reduced Ejection Fraction
Detailed description
Heart failure with reduced ejection fraction (HFrEF) remains a major cause of morbidity, mortality, and healthcare utilization despite advances in guideline-directed medical therapy. Patients who experience worsening heart failure events, including hospitalization or the need for urgent outpatient treatment, remain at increased risk of recurrent cardiovascular events and represent a high-risk population requiring additional therapeutic strategies.
The nitric oxide-soluble guanylate cyclase (NO-sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in maintaining cardiovascular function. In heart failure, endothelial dysfunction and reduced nitric oxide bioavailability may impair this pathway, contributing to vascular dysfunction, myocardial remodeling, and disease progression.
Vericiguat is an oral soluble guanylate cyclase stimulator that enhances cGMP production by directly stimulating soluble guanylate cyclase and increasing its sensitivity to endogenous nitric oxide. This mechanism provides a novel therapeutic approach that differs from conventional heart failure treatments targeting neurohormonal pathways.
Previous clinical evidence, including the VICTORIA trial, demonstrated that vericiguat reduced the risk of cardiovascular death or first hospitalization for heart failure among patients with chronic heart failure and recent worsening heart failure events. However, further evaluation of its effectiveness and safety in specific clinical settings and populations remains important.
This randomized, placebo-controlled, double-blind clinical trial will evaluate the effectiveness and safety of vericiguat in patients with heart failure with reduced ejection fraction receiving standard medical therapy. The study aims to determine whether the addition of vericiguat provides further clinical benefit compared with standard therapy alone in this high-risk patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Vericiguat tabletVericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care |
| Placebo | Placebo comparator | Drug: PlaceboStandard of care medications with placebo. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >18 years of any gender
- Chronic heart failure (New York Heart Association [NYHA] functional class II, III, or IV), a reduced left ventricular ejection fraction of less than 45% within 12 months before randomization
- Elevated natriuretic peptide level: (For patients in sinus rhythm, the criteria include a plasma B-type natriuretic peptide (BNP) level of at least 300 pg per milliliter or an NT-proBNP level of at least 1000 pg per milliliter. For patients in atrial fibrillation, the criteria included a BNP level of at least 500 pg per milliliter or an NT-proBNP level of at least 1600 pg per milliliter).
- Evidence of worsening heart failure.
- The percentage of enrolled patients with an estimated glomerular filtration rate of 15 to 30 ml per minute per 1.73 m2 of body-surface area was capped at 15%.
Key exclusion criteria (5 listed)
- Systolic blood pressure of less than 100 mm Hg.
- Concurrent or anticipated use of long-acting nitrates.
- Use of intravenous inotropes or implantable left ventricular assist devices.
- Not on standard of care medical treatment for heart failure.
- Unwillingness to give consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vericiguat tabletAlso: VERIZOTVericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care | Drug | Treatment |
| PlaceboAlso: VERIZOTParticipants will receive a matching placebo tablet. The placebo will follow the same dosing schedule as the study drug (2.5 mg, 5 mg, and 10 mg) to maintain blinding. | Drug | Placebo |
Primary outcome
Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Time frame: Baseline to Month 6
The Kansas City Cardiomyopathy Questionnaire (KCCQ-12) is a validated, patient-reported instrument that assesses health status, including symptoms, physical limitations, social limitations, and quality of life in patients with heart failure. The Overall Summary Score ranges from 0 to 100, with higher scores indicating better health status. The primary endpoint is the change in the KCCQ-12 Overall Summary Score from baseline to Month 6.
1 secondary outcome
First Hospitalization for Heart Failure
Time frame: From enrollment to Month 6
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ghazala Irfan, FCPS principal investigator
National Institute of Cardiovascular Diseases Karachi, Pakistan
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vericiguat tablet in people with Heart Failure With Reduced Ejection Fraction (HFrEF), run by National Institute of Cardiovascular Diseases, Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ghazala Irfan, FCPS (+92 3002167206, ghazala.irfan@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ-12) (time frame: Baseline to Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.