Clinical trial NCT03962855: Thromboxane Receptor Antagonist to Improve Endothelial Function
Official title: The Thromboxane Receptor Antagonist to Block the Effects of Non-Platelet Thromboxane Generation and Improve Endothelial Function (TRAP) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Vascular Dilation
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: Cumberland Pharmaceuticals
First posted: 2019-05-24
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single center, prospectively randomized, double-blinded, placebo-controlled clinical trial.
Primary purpose: TREATMENT

Brief 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 matching placebo for the 4 week study period.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Reactive Hyperemia Index (RHI)
timeFrame: Baseline to 4 weeks
Secondary outcomes:
measure: Change in Percent Flow-mediated Vasodilation (FMD)
timeFrame: Baseline to 4 weeks
measure: Change in Urinary TXB2-M
timeFrame: Baseline to 4 weeks
Other outcomes:
Locations:
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
Study officials:
affiliation: University of Massachusetts, Worcester
name: Jeffrey J Rade, MD
role: PRINCIPAL_INVESTIGATOR
References: