Heart Failure With Reduced Ejection Fraction (HFrEF)
Conditions
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
Brief summary
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.
Interventions
Vericiguat 10 mg (titrated from 2.5 mg, to 5 mg, and to 10 mg), on a background of standard of care
DRUGPlacebo
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.
Sponsors
National Institute of Cardiovascular Diseases, Pakistan
Horizon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age \>18 years of any gender 2. 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 3. 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). 4. Evidence of worsening heart failure. 5. 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%. 6. Patients on guideline-based medical therapy 3 months 7. Written and informed consent.
Exclusion criteria
1. Systolic blood pressure of less than 100 mm Hg. 2. Concurrent or anticipated use of long-acting nitrates. 3. Use of intravenous inotropes or implantable left ventricular assist devices. 4. Not on standard of care medical treatment for heart failure. 5. Unwillingness to give consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life using Kansas City Cardiomyopathy Questionnaire (KCCQ-12) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Hospitalization for Heart Failure | From enrollment to Month 6 | Time to first hospitalization for worsening heart failure during the study follow-up. |
Contacts
CONTACTGhazala Irfan, FCPS
CONTACTReema Qayoom, FCPS
PRINCIPAL_INVESTIGATORGhazala Irfan, FCPS
National Institute of Cardiovascular Diseases Karachi, Pakistan
Outcome results
None listed