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

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

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Implantation of a bare metal stent

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Charite University Hospital
  • Saarland
    • Homburg/Saar, Saarland, Germany, 66421
      • UniversitY Hospital of Saarland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Saarland
• Investigators: Principal Investigator: Bruno Scheller, MD, University Hospital, Saarland; Principal Investigator: Wolfgang Rutsch, MD, Charite Hospital, Berlin

Study record dates

Study Major Dates

• Study Start: March 1, 2003
• Primary Completion (Actual): June 1, 2004
• Study Completion (Actual): June 1, 2004

Study Registration Dates

• First Submitted: June 7, 2010
• First Submitted That Met QC Criteria: June 8, 2010
• First Posted (Estimate): June 9, 2010

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: paclitaxel; stent; stent implantation; contrast media
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: 1-325-02