Sildenafil To Prevent Clot

NCT03199612 | Completed Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2016-74045K23HL145140
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The advent of continuous flow (CF) pumps for patients with severe heart failure has led to marked improvements in survival; however, pump operation remains fraught with adverse thrombotic events. This climbing rate of thrombosis and stroke during CF pump support has led to a recent warning by the US Food and Drug Administration. Despite a rising incidence of pump thrombosis and its downstream complications of stroke, the hematologic mechanisms behind these devastating adverse events remain uncertain. Recently, it has been recognized that CF pump induced hemolysis precedes and is associated with thrombosis. In-vitro studies show increased platelet function with exposure to products of hemolysis, which is also known to occur in diseases of intravascular hemolysis such as sickle cell anemia. This proposal will investigate if hemolysis associated increased platelet function can be reduced by a potentiation of nitric oxide signaling by an oral phosphodiesterase-5 inhibitor, sildenafil. Elucidating mechanisms of hemolysis induced thrombosis may inform best strategies for prevention of end organ damage and maintaining optimal CF pump operation.

Conditions

Thrombosis; Hemolysis

Keywords

Thrombosis during Continuous Flow Pump Support

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve for Adenosine Diphosphate (ADP)

  During the study period platelet activation and aggregation will be measured from drawn blood samples. Platelet rich plasma will be isolated from these samples and platelet aggregometry will be used to measure platelet activation and aggregation. Platelet activation and aggregation is measured as an area under the curve (AUC) derived as the resistance (ohms) x time (s). There is no reference range for ADP induced AUC. Higher values of AUC indicate greater platelet aggregation.

  Baseline, day 8 and day 15

Secondary Outcomes (2)

• Pro-thrombotic Inflammation as Measured by High-sensitivity C-reactive Protein (hs CRP)

  Baseline, day 8 and day 15

• Pro-thrombotic Inflammation as Measured by Fibrinogen

  Baseline, day 8 and day 15

Other Outcomes (2)

• Serum Angiopoietin-2 to Angiopoietin-1 Ratio

  Baseline, day 8 and day 15

• Concentration of Serum Endothelin-1

  Baseline, day 8 and day 15

Study Arms (2)

Sildenafil

ACTIVE COMPARATOR

Baseline blood samples and study measurements will be acquired. Then 20 mg of the study drug will be administered. Then BP will be recorded every 30 minutes for two hours. If BP is stable (drop is \< 5 mmHg after 2 hours and patient is asymptomatic), patient will proceed to take 20 mg of the study drug every 8 hours. The patient will return to clinic on day 8 and 20 mg of the study drug will be administered. After 2 hours blood samples and study measurements will be collected and the patient will resume 20 mg of the study for the next two doses. The patient will return for a third clinic visit on the next day and if BP is in the acceptable range, 40 mg of the study drug will be administered. If BP remains stable for 2 hours, then the patient will continue taking 40 mg every 8 hours. The patient will return to clinic on day 15 for a final study visit and will be given the last 40 mg dose of the study drug and after 2 hours blood samples and study measurements will be taken.

Drug: Sildenafil

Placebo Oral Tablet

PLACEBO COMPARATOR

Negative control to understand the potential changes in platelet activation and aggregation in comparison to sildenafil.

Drug: Placebo Oral Tablet

Interventions

Sildenafil DRUG

To conduct a randomized placebo controlled study to test the hypothesis that platelet activation and aggregation during ongoing low level hemolysis in outpatients on chronic CF pump support can be reduced by sildenafil.

Also known as: Viagra, Revatio

Sildenafil

Placebo Oral Tablet DRUG

Negative control to understand the potential changes in platelet activation adn aggregation in comparison to sildenafil.

Also known as: Sildenafil matching placebo

Placebo Oral Tablet

Eligibility Criteria

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

You may qualify if:

• Adult outpatients (≥18 years old) with ongoing durable CF pump support.

You may not qualify if:

• Taking sildenafil or nitrates for clinical indications
• Ongoing infection
• Unwilling or unable to give written, informed consent

Sponsors & Collaborators

• Montefiore Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Thrombosis; Hemolysis

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Omar Saeed
• Organization: Montefiore Einstein

osaeed@montefiore.org

718-920-2626

Study Officials

• Omar Saeed, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Placebo controlled randomized trial with 1:1 enrollment in each study arm.

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 27, 2017
• Study Start: June 3, 2019
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: July 10, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)