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

April 25, 2023 updated by: University Hospital, Saarland

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo control
Contrast medium without Paclitaxel
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 0.85 mg
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 4.27 mg
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 8.54 mg
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 17.08 mg
Bare Metal Stent

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Late lumen loss
Time Frame: 6 months
Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention
6 months
Restenosis rate
Time Frame: 6 months
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)
Time Frame: 6 months
  1. Abrupt and sub-abrupt closure
  2. Target lesion revascularization
  3. Myocardial infarction
  4. Death
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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