The Thromboxane Receptor Antagonist to Block the Effects of Non-Platelet Thromboxane Generation and Improve Endothelial Function (TRAP) Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Change in Reactive Hyperemia Index (RHI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Ifetroban
Ifetroban 250 mg oral capsule administered once daily for a minimum of 4 weeks.
干预措施: Ifetroban Sodium (Drug)
Placebo
Matching placebo administered once daily for a minimum of 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Reactive Hyperemia Index (RHI)
时间窗: Baseline to 4 weeks
The change in Reactive Hyperemia Peripheral Index (RHI) as measured by Arterial Tonometry. The Reactive Hyperemia Index (RHI) is calculated as the ratio of post- to pre-occlusion peripheral arterial tone signals on the occluded side, normalized to the control side, and further adjusted for baseline vascular tone. RHI is automatically measured by the EndoPAT 2000 software. According to the manufacturer, an RHI value greater than 1.67 is considered normal, while a lower value indicates endothelial dysfunction and is associated with an increased risk of cardiovascular events.
次要结局
- Change in Percent Flow-mediated Vasodilation (FMD)(Baseline to 4 weeks)
- Change in Urinary TXB2-M(Baseline to 4 weeks)
研究者
Jeffrey Rade
Professor
University of Massachusetts, Worcester