Clinical trial NCT01140204: Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media
Official title: Restenosis Inhibition by Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Coronary Artery Disease
Keywords: stent
contrast media
paclitaxel
stent implantation
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2010-06-09
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety of intracoronary application
timeFrame: ca. 30 minutes (during intervention)
Secondary outcomes:
measure: Late lumen loss
timeFrame: 6 months
measure: Restenosis rate
timeFrame: 6 months
measure: Combined clinical endpoints (Major adverse cardiac events, MACE)
timeFrame: 6 months
Other outcomes:
Locations:
city: Homburg/Saar
country: Germany
facility: University Hospital of Saarland
state: Saarland
city: Berlin
country: Germany
facility: Charite University Hospital
Study officials:
affiliation: University Hospital, Saarland
name: Bruno Scheller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite Hospital, Berlin
name: Wolfgang Rutsch, MD
role: PRINCIPAL_INVESTIGATOR
References: