The Effect of Vericiguat on Peripheral Vascular Function, Patient Health Status and Inflammation

NCT05420012 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB_00152530
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

The concept that direct stimulation of soluble guanylate cyclase (sGC) could be a particularly effective approach to increase cyclic guanosine monophosphate (cGMP) in conditions of increased inflammation/oxidative stress, endothelial dysfunction, and reduced nitric oxide (NO) bioavailability. Thus, the aim of the proposed study is to examine the effect of Vericiguat on peripheral vascular function, inflammatory status, and patient health status. The study also aims to identify patients who are particularly likely to benefit from Vericiguat treatment and predict that these patients will be defined by baseline peripheral vascular dysfunction and high inflammatory state.

Conditions

Heart Failure; Heart Failure With Reduced Ejection Fraction (HFrEF)

Outcome Measures

Primary Outcomes (1)

• Flow-Mediated Dilation (FMD)

  Change in vascular function using flow-mediated vasodilation (FMD) test. FMD is quantified as the maximal change in brachial artery diameter following cuff release, expressed as a percentage increase from pre-occlusion values (%FMD).

  Baseline to 12 weeks

Secondary Outcomes (5)

• Six-minute Walk Test (6MWT)

  Baseline to 12 weeks

• Kansas City Cardiomyopathy Questionnaire-12(KCCQ12)

  Baseline to 12 weeks

• Visual Analogue Scale (VAS)

  Baseline and 12 weeks

• Inflammatory Biomarkers Serum Interleukin-18 (IL-18)

  Baseline and 12 weeks

• Inflammatory Biomarkers Serum Interleukin-6 (IL-6)

  Baseline and 12 weeks

Study Arms (2)

Vericiguat

EXPERIMENTAL

Study drug

Drug: Vericiguat

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Vericiguat DRUG

A starting dose of vericiguat 2.5 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Subjects will be up-titrated in a blinded fashion to 5 mg and then to the target dose of 10 mg of vericiguat or matching placebo using titration criteria based on mean systolic blood pressure(SBP) evaluation and clinical symptoms at 2 week intervals. Titration to 10 mg in subjects who have not yet reached the target dose is intended at every visit/phone call throughout the study duration based on mean SBP measurement and safety considerations, at the discretion of the investigator.

Also known as: VERQUVO

Vericiguat

Placebo DRUG

A starting dose of vericiguat 2.5 mg or matching placebo will be initiated after randomization and completion of the baseline testing. Subjects will be up-titrated in a blinded fashion to 5 mg and then to the target dose of 10 mg of vericiguat or matching placebo using titration criteria based on mean systolic blood pressure(SBP) evaluation and clinical symptoms at 2 week intervals. Titration to 10 mg in subjects who have not yet reached the target dose is intended at every visit/phone call throughout the study duration based on mean SBP measurement and safety considerations, at the discretion of the investigator.

Also known as: Control group

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of chronic symptomatic HF (ACC/AHA Class C) and New York Heart Association (NYHA) Class II or III symptoms at the time of enrollment.
• Left ventricular ejection fraction (LVEF) of ≤45% assessed within 12 months prior to randomization by any imaging method.
• Systemic blood pressure ≥90/60 mmHg.
• Standard guideline-directed HF therapy.
• If female of reproductive potential, agrees to avoid becoming pregnant while receiving study drug and for 14 days after the last dose of study drug by complying with abstinence from heterosexual activity or use (or have her partner use) contraception during heterosexual activity.

You may not qualify if:

• Addition of a new disease-modifying HF pharmacotherapy or CRT-D in previous 4 weeks.
• Current or anticipated use of long-acting nitrates or nitric oxide (NO) donors including isosorbide dinitrate, isosorbide 5-mononitrate, pentaerythritol tetranitrate, nicorandil or transdermal nitroglycerin (NTG) patch, and molsidomine.
• Current or anticipated use of phosphodiesterase type 5 (PDE5) inhibitors such as vardenafil, tadalafil, and sildenafil.
• Current use or anticipated use of a soluble guanylate cyclase (sGC) stimulator such as riociguat.
• Known allergy or sensitivity to any sGC stimulator.
• Estimated glomerular filtration rate (eGFR) \<15 mL/min/1.73 m2 or chronic dialysis.
• Patients who are pregnant or breastfeeding or plan to become pregnant or to breastfeed.

Sponsors & Collaborators

• Josef Stehlik: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Veterans Affairs Salt Lake City Health Care System (VAMC)

Salt Lake City, Utah, 84148, United States

Location

MeSH Terms

Conditions

Heart Failure

Interventions

vericiguat; Control Groups

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Results Point of Contact

• Title: Josef Stehlik
• Organization: University of Utah

josef.stehlik@hsc.utah.edu

801-585-9797

Study Officials

• Josef Stehlik, M.D, M.P.H.

  University of Utah Health Science Center & Veterans Affairs Salt Lake City Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Patients will be assigned with equal allocation to the intervention and control groups using block randomization to ensure a balance in sample size across groups over time.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Division of Cardiovascular Medicine

Model Details: Randomized double-blind, placebo-controlled study in patients with heart failure \[HF\] with reduced ejection fraction \[HFrEF\].

Study Record Dates

• First Submitted: June 11, 2022
• First Posted: June 15, 2022
• Study Start: May 1, 2023
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: October 8, 2025
• Results First Posted: October 8, 2025

Record last verified: 2025-09

Locations

US (2)