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

Coronary Artery Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01140204
• Other study ID #: 1-325-02
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2003
• Est. completion date: June 2004

Study information

• Verified date: April 2023
• Source: Universität des Saarlandes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: June 2004
• Est. primary completion date: June 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease

Intervention

Device:
• Implantation of a bare metal stent
Bare Metal Stent

Locations

Country	Name	City	State
Germany	Charite University Hospital	Berlin
Germany	University Hospital of Saarland	Homburg/Saar	Saarland

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Saarland

Country where clinical trial is conducted

Germany, 

Outcome

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