Thromboxane Receptor Antagonist to Improve Endothelial Function (TRAP)

Jeffrey Rade

Status and phase

Completed

Phase 2

Conditions

Cardiovascular Diseases

Vascular Dilation

Treatments

Drug: Ifetroban Sodium

Drug: 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 matching 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

57 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Males and females 18-80 years of age with established cardiovascular disease
Take >=81 mg daily of aspirin as part of their daily medical regimen
Urine thromboxane B2 metabolites >1145 pg/mg creatinine on screening.
Able to provide written consent and comply with protocol-specific procedures.

Exclusion criteria

Chronic oral anticoagulation with a non-vitamin K antagonist.
Anticipated change or interruption in aspirin therapy during the study period.
ST segment myocardial infarction within the past 30 days.
Cardiac surgery within the past 30 days.
Stage 4-5 renal failure or on renal replacement therapy.
An ongoing uncontrolled severe inflammatory condition.
Pregnant,intending to become pregnant or breast feeding.
Known ifetroban or aspirin sensitivity Inability to perform vascular testing.
Participation in another investigational drug trial within 30 days of randomization.