Sildenafil to Reduce Vascular Remodeling During Left Ventricular Assist Device Support

NCT ID: NCT06510322

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-12
• Study Completion Date: 2029-12-31

Brief Summary

Contemporary left ventricular assist device (LVAD) therapy improves survival during advanced heart failure but vascular aging develops rapidly leading to major adverse events including stroke and bleeding in nearly half of patients. In this study, the study team aims to investigate whether sildenafil pharmacotherapy, which has anti-fibrotic effects, can reduce vascular aging during LVAD support. An aim of this study is to compare changes in small blood vessels in the gastrointestinal tract between participants receiving sildenafil or placebo. Video capsule endoscopy (VCE) will be used to assess these changes in small blood vessels.

Detailed Description

Over 6.5 million individuals in the United States suffer from heart failure (HF), with the burden of this disease expected to grow over the next decade. Approximately 300,000 of these patients have advanced HF and may benefit from durable left ventricular assist device (LVAD) therapy, which can improve outcomes during advanced HF. However, despite advancements in device design that have increased survival rates, large registries of real- world cases reveal that nearly half of patients experience severe vascular adverse events, including stroke and bleeding, during prolonged contemporary LVAD support. This elevated adverse-event rate remains a major barrier to safely expanding the use and durability of LVAD therapy. Vascular remodeling or aging of the large and small blood vessels is known to promote stroke and bleeding within the general population. Critically, such remodeling is rapidly accelerated under conditions of reduced pulsatility produced by LVADs, evidenced by large vessel stiffening and fibrosis, small vessel angiodysplasia, and endothelial dysfunction. Phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, are prescribed to select LVAD patients with pulmonary hypertension and right heart failure. However, given that these agents enhance nitric oxide-cGMP signaling in platelets and vascular smooth muscle cells, leading to anti-thrombotic and anti-fibrotic effects, they may also reduce vascular remodeling and related adverse events. Here, based on preliminary findings, a double-blind, randomized, placebo-controlled trial will be conducted to determine the effects of chronic sildenafil administration on vascular remodeling during LVAD support.

Conditions

Vascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Sildenafil

Participants in this arm will receive sildenafil 20mg every 8 hours for 1 week and then dose will be up titrated to 40mg every 8 hours for the duration of the study period.

Group Type: ACTIVE_COMPARATOR

Sildenafil

Intervention Type: DRUG

Orally administered phosphodiesterase-5 (PDE-5) inhibitor, which enhances nitric oxide signaling in platelets and blood vessels.

Placebo

Participants in this arm will receive matching placebo, which serves as a negative control to understand changes in small and large blood vessels.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Matched capsule not containing any medication

Interventions

Sildenafil

Orally administered phosphodiesterase-5 (PDE-5) inhibitor, which enhances nitric oxide signaling in platelets and blood vessels.

Intervention Type: DRUG

Placebo

Matched capsule not containing any medication

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Over 18 years of age
• Supported by a durable LVAD or planned to undergo placement of a durable LVAD
• Be able to give informed consent

Exclusion Criteria

• History of pre-existing aortic valve prosthesis or an aortic graft
• Allergy to sildenafil
• Taking any nitric oxide (NO) donor medications
• History of complete carotid occlusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Omar Saeed, MD

Role: PRINCIPAL_INVESTIGATOR

Montefiore Medical Center

Locations

Montefiore Medical Center

The Bronx, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Omar Saeed, MD

Role: CONTACT

osaeed@montefiore.org

718-920-2626

Lorenzo D'Angelo, MD

Role: CONTACT

718-920-2626

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Other Identifiers

1R01HL172972

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2024-16098

Identifier Type: -

Identifier Source: org_study_id