Coronary Artery Disease
Conditions
Keywords
stent, contrast media, paclitaxel, stent implantation
Brief summary
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
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.
Interventions
DEVICEImplantation of a bare metal stent
Bare Metal Stent
Sponsors
University Hospital, Saarland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of intracoronary application | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Late lumen loss | 6 months | Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention |
| Restenosis rate | 6 months | Defined as a diameter stenosis of ≥50% (assessed by quantitative coronary angiography) at any control angiography |
| Combined clinical endpoints (Major adverse cardiac events, MACE) | 6 months | 1. Abrupt and sub-abrupt closure 2. Target lesion revascularization 3. Myocardial infarction 4. Death |
Countries
Germany
Outcome results
None listed