NCT06510322

Sildenafil to Reduce Vascular Remodeling During Left Ventricular Assist Device Support

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Montefiore Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	Sildenafil	Orally administered phosphodiesterase-5 (PDE-5) inhibitor, which enhances nitric oxide signaling in platelets and blood vessels.
OTHER	Placebo	Matched capsule not containing any medication

Timeline

• Start date: 2025-03-12
• Primary completion: 2029-12-01
• Completion: 2029-12-01
• First posted: 2024-07-19
• Last updated: 2026-01-23

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study