Thromboxane Receptor Antagonist to Improve Endothelial Cell Function (TRAP)

Jeffrey Rade

Status and phase: Active, not recruiting; Phase 2

Conditions: Cardiovascular Diseases; Vascular Dilation

Treatments: Drug: Ifetroban Sodium; Other: Placebo

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03962855

UMMS-TPRA-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

Ifetroban

Active Comparator group

Description:

Ifetroban 250 mg oral capsule administered once daily for a minimum of 4 weeks.

Treatment:

Drug: Ifetroban Sodium

Placebo

Placebo Comparator group

Description:

Matching placebo administered once daily for a minimum of 4 weeks.

Treatment:

Other: Placebo