Restenosis Inhibition by Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Safety of intracoronary application
研究概览
简要总结
This was a randomized, placebo-controlled, multi-centre study, double-blind within each dose level, with four ascending dose levels to test the tolerability and safety of iopromide-paclitaxel in patients with de novo lesions in coronary arteries. Thirty-two patients were included into the trial, which were divided into four treatment groups. A total of four concentration levels of paclitaxel-iopromide concentrations were investigated. In each treatment group, six patients received iopromide-paclitaxel and two patients placebo (iopromide without paclitaxel). In each patient, the doses were adjusted individually as needed.
详细描述
Background: Non-stent-based immediate release formulations of paclitaxel have been shown to reduce in-stent restenosis in animal experiments and initial clinical trials. Paclitaxel dissolved in the angiographic contrast agent iopromide was well tolerated and inhibited neointimal proliferation in a dose-dependent manner after injection into porcine coronary arteries.
Methods: As a first step in entering clinical development, a phase I trial was performed using 4 ascending paclitaxel dose/concentration levels: samples of up to 100 ml of the contrast agent containing 10, 50, 100 or 200 μM paclitaxel were randomly administered to 6 adult patients each assigned to bare metal stent implantation for single de novo coronary artery lesions, while 8 patients treated with plain contrast medium served as controls. Safety variables and tolerability as well as angiographic parameters were assessed.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male and postmenopausal female patients
- •aged 18 years and older
- •clinical evidence of stable or unstable angina, a positive functional test and a stentable de novo lesion in a native coronary artery
- •diameter stenosis > 70% (visual estimate), lesion length < 25 mm, and a vessel diameter ≥ 2.5 mm.
排除标准
- •acute myocardial infarction
- •left ventricular ejection fraction of < 30%
- •aorto-ostial lesion
- •unprotected left main lesion or a bypass graft
- •clear angiographic calcification in the target lesion
- •visible thrombus proximal to the lesion
- •chronic total occlusion
- •platelet count <100,000 cells/mm3 or >700,000 cells/mm3
- •WBC <3,000 cells/mm3
- •known hypersensitivity or contraindication to aspirin, heparin, clopidogrel, abciximab, paclitaxel, stainless steel
- •sensitivity to contrast media not amenable to adequate premedication
- •medical illness (i.e. cancer, liver disease or congestive heart failure) associated with a life expectancy of less than two years
研究组 & 干预措施
Placebo control
Contrast medium without Paclitaxel
干预措施: Implantation of a bare metal stent (Device)
Iopromide Paclitaxel 0.85 mg
Iopromide Paclitaxel 0.85 mg
干预措施: Implantation of a bare metal stent (Device)
Iopromide Paclitaxel 4.27 mg
Iopromide Paclitaxel 4.27 mg
干预措施: Implantation of a bare metal stent (Device)
Iopromide Paclitaxel 8.54 mg
Iopromide Paclitaxel 8.54 mg
干预措施: Implantation of a bare metal stent (Device)
Iopromide Paclitaxel 17.08 mg
Iopromide Paclitaxel 17.08 mg
干预措施: Implantation of a bare metal stent (Device)
结局指标
主要结局
Safety of intracoronary application
时间窗: ca. 30 minutes (during intervention)
* Continuous monitoring electrocardiogram (ECG) * Vital signs * Invasive measure of blood pressure * Lab variables: red blood count, white blood count, diff, creatinine kinase, creatinine kinase - muscle bound, creatinine * Cmax of paclitaxel in serum * 12-lead ECG * Adverse events
次要结局
- Late lumen loss(6 months)
- Restenosis rate(6 months)
- Combined clinical endpoints (Major adverse cardiac events, MACE)(6 months)