Thromboxane Receptor Antagonist to Improve Endothelial Cell Function

Cardiovascular Diseases Clinical Trial

— TRAP  

Official title:

The Thromboxane Receptor Antagonist to Blunt the Effects of Non-Platelet Thromboxane Generation and Improve Endothelial Cell Function (TRAP) Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03962855
• Other study ID #: UMMS-TPRA-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 20, 2019
• Est. completion date: June 1, 2024

Study information

• Verified date: January 2024
• Source: University of Massachusetts, Worcester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates whether addition of the thromboxane receptor antagonist to chronic aspirin therapy improves endothelial function and reduces non-platelet thromboxane generation in patients with established cardiovascular disease. Half of participants will receive ifetroban and the other half will receive matchcing placebo for the 4 week study period.

Description:

Thromboxane is a prostaglandin produced in healthy individuals mainly in platelets, where it mediates platelet activation and vasoconstriction via binding to cellular thromboxane-prostanoid (TP) receptors. The cardioprotective effect of aspirin is due to suppression of platelet thromboxane generation and reactivity. Unfortunately 25-50% of patients with cardiovascular disease taking ASA continue to generate thromboxane from non-platelet sources, which significantly increases their risk of atherothrombosis and death. Evidence suggests that oxidative stress is a potent stimulus for thromboxane generation in endothelial cells that involves autocrine/paracrine signaling through the TP receptor. This clinical trial addresses the central hypothesis that vascular endothelial cells under oxidative stress are a major source of non-platelet thromboxane generation in patients with cardiovascular disease and that antagonism of the TP receptor will suppress its formation and improve endothelial function.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: June 1, 2024
• Est. primary completion date: November 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Males and females =18 years of age with established cardiovascular disease
• Take 81 mg daily of aspirin as part of their daily medical regimen
• Urine thromboxane B2 metabolites >1500 pg/mg creatinine on screening.
• Able to provide written consent and comply with protocol-specific procedures.

Exclusion Criteria:

• Chronic oral anticoagulation.
• ST segment myocardial infarction within 1 month.
• Cardiac surgery within 1 month.
• Ongoing uncontrolled severe inflammatory condition.
• Pregnant or lactating.
• Ifetroban or aspirin sensitivity
• Inability to perform vascular testing.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Vascular Dilation

Intervention

Drug:
• Ifetroban Sodium
Ifetroban sodium 250 mg capsule once daily for 4 weeks

Other:
• Placebo
Placebo arm to match Ifetroban Sodium once daily for 4 weeks.

Locations

Country	Name	City	State
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Jeffrey Rade	American Heart Association, Cumberland Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Oxidative stress	Change in urine 8-isoPGF2a	Baseline to 4 weeks
Other	Renal Prostanoid Excretion	Change in urine TXB2, 6-ketoPGF1a and the ratio of TXB2 to 6-ketoPGF1a,	Baseline to 4 weeks
Other	Prostacyclin Generation	Change in urine 2,3-dinor-6-ketoPGF1a and ratio of 11-dhTXB2 to 2,3-dinor-6-ketoPGF1a	Baseline to 4 weeks
Other	Inflammatory Markers	Change in hs-CRP and ICAM-1	Baseline to 4 weeks
Other	Coagulation Markers	Change in soluble tissue factor and activated protein C	Baseline to 4 weeks
Other	Renal Function	Change in eGFR	Baseline to 4 weeks
Other	Cardiac Function	Change in NT pro-BNP	Baseline to 4 weeks
Primary	Peripheral Arterial Tonometry	Change in Reactive Hyperemia Index (RHI)	Baseline to 4 weeks
Secondary	Brachial vasoractivity	Change in Percent flow-mediated vasodilation (FMD)	Baseline to 4 weeks
Secondary	Non-platelet thromboxane generation	Change in urine 11-dehydrothromboxane B2	Baseline to 4 weeks