Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Restenosis Inhibition by Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Implantation of a bare metal stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo control<br>Contrast medium without Paclitaxel | Device: Implantation of a bare metal stent<br>* Bare Metal Stent<br>|
| Active Comparator: Iopromide Paclitaxel 0.85 mg<br>Iopromide Paclitaxel 0.85 mg | Device: Implantation of a bare metal stent<br>* Bare Metal Stent<br>|
| Active Comparator: Iopromide Paclitaxel 4.27 mg<br>Iopromide Paclitaxel 4.27 mg | Device: Implantation of a bare metal stent<br>* Bare Metal Stent<br>|
| Active Comparator: Iopromide Paclitaxel 8.54 mg<br>Iopromide Paclitaxel 8.54 mg | Device: Implantation of a bare metal stent<br>* Bare Metal Stent<br>|
| Active Comparator: Iopromide Paclitaxel 17.08 mg<br>Iopromide Paclitaxel 17.08 mg | Device: Implantation of a bare metal stent<br>* Bare Metal Stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of intracoronary application | 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 | ca. 30 minutes (during intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Late lumen loss | Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention | 6 months | 
| Restenosis rate | Defined as a diameter stenosis of ≥50% (assessed by quantitative coronary angiography) at any control angiography | 6 months | 
| Combined clinical endpoints (Major adverse cardiac events, MACE) | Abrupt and sub-abrupt closure Target lesion revascularization Myocardial infarction Death | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stent, contrast media, paclitaxel, stent implantation