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

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Saarland
ClinicalTrials.gov Identifier:
NCT01140204
First received: June 7, 2010
Last updated: June 8, 2010
Last verified: June 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
 Device: Implantation of a bare metal stent
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Restenosis Inhibition by Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Hospital, Saarland:

Primary Outcome Measures:
  • Safety of intracoronary application [ Time Frame: ca. 30 minutes (during intervention) ] [ Designated as safety issue: Yes ]
    • 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 Outcome Measures:
  • Late lumen loss [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention

  • Restenosis rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Defined as a diameter stenosis of ≥50% (assessed by quantitative coronary angiography) at any control angiography

  • Combined clinical endpoints (Major adverse cardiac events, MACE) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    1. Abrupt and sub-abrupt closure
    2. Target lesion revascularization
    3. Myocardial infarction
    4. Death


Enrollment: 32
Study Start Date: March 2003
Study Completion Date: June 2004
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Iopromide Paclitaxel 0.85 mg
 Device: Implantation of a bare metal stent
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 4.27 mg
Iopromide Paclitaxel 4.27 mg
 Device: Implantation of a bare metal stent
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 8.54 mg
Iopromide Paclitaxel 8.54 mg
 Device: Implantation of a bare metal stent
Bare Metal Stent
Active Comparator: Iopromide Paclitaxel 17.08 mg
Iopromide Paclitaxel 17.08 mg
 Device: Implantation of a bare metal stent
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01140204

Locations
Germany
University Hospital of Saarland
Homburg/Saar, Saarland, Germany, 66421
Charite University Hospital
Berlin, Germany, 10117
Sponsors and Collaborators
University Hospital, Saarland
Investigators
Principal Investigator: Bruno Scheller, MD University Hospital, Saarland
Principal Investigator: Wolfgang Rutsch, MD Charite Hospital, Berlin
  More Information

No publications provided

Responsible Party: Bruno Scheller, MD, University Hospital, Saarland
ClinicalTrials.gov Identifier: NCT01140204     History of Changes
Other Study ID Numbers: 1-325-02
Study First Received: June 7, 2010
Last Updated: June 8, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University Hospital, Saarland:
stent
contrast media
paclitaxel
stent implantation

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Antineoplastic Agents
 Paclitaxel
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 22, 2013