Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media
Primary Purpose
Coronary Artery Disease
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Implantation of a bare metal stent
Sponsored by

About this trial
This is an interventional treatment trial for Coronary Artery Disease focused on measuring stent, contrast media, paclitaxel, stent implantation
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
Sites / Locations
- University Hospital of Saarland
- Charite University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Placebo Comparator
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Placebo control
Iopromide Paclitaxel 0.85 mg
Iopromide Paclitaxel 4.27 mg
Iopromide Paclitaxel 8.54 mg
Iopromide Paclitaxel 17.08 mg
Arm Description
Contrast medium without Paclitaxel
Iopromide Paclitaxel 0.85 mg
Iopromide Paclitaxel 4.27 mg
Iopromide Paclitaxel 8.54 mg
Iopromide Paclitaxel 17.08 mg
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Late lumen loss
Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention
Restenosis rate
Defined as a diameter stenosis of ≥50% (assessed by quantitative coronary angiography) at any control angiography
Combined clinical endpoints (Major adverse cardiac events, MACE)
Abrupt and sub-abrupt closure
Target lesion revascularization
Myocardial infarction
Death
Full Information
NCT ID
NCT01140204
First Posted
June 7, 2010
Last Updated
April 25, 2023
Sponsor
University Hospital, Saarland
1. Study Identification
Unique Protocol Identification Number
NCT01140204
Brief Title
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
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
March 2003 (undefined)
Primary Completion Date
June 2004 (Actual)
Study Completion Date
June 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Saarland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease
Keywords
stent, contrast media, paclitaxel, stent implantation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo control
Arm Type
Placebo Comparator
Arm Description
Contrast medium without Paclitaxel
Arm Title
Iopromide Paclitaxel 0.85 mg
Arm Type
Active Comparator
Arm Description
Iopromide Paclitaxel 0.85 mg
Arm Title
Iopromide Paclitaxel 4.27 mg
Arm Type
Active Comparator
Arm Description
Iopromide Paclitaxel 4.27 mg
Arm Title
Iopromide Paclitaxel 8.54 mg
Arm Type
Active Comparator
Arm Description
Iopromide Paclitaxel 8.54 mg
Arm Title
Iopromide Paclitaxel 17.08 mg
Arm Type
Active Comparator
Arm Description
Iopromide Paclitaxel 17.08 mg
Intervention Type
Device
Intervention Name(s)
Implantation of a bare metal stent
Intervention Description
Bare Metal Stent
Primary Outcome Measure Information:
Title
Safety of intracoronary application
Description
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
Time Frame
ca. 30 minutes (during intervention)
Secondary Outcome Measure Information:
Title
Late lumen loss
Description
Difference between angiographic in-stent minimum lumen diameter at 6 months follow-up and post-intervention
Time Frame
6 months
Title
Restenosis rate
Description
Defined as a diameter stenosis of ≥50% (assessed by quantitative coronary angiography) at any control angiography
Time Frame
6 months
Title
Combined clinical endpoints (Major adverse cardiac events, MACE)
Description
Abrupt and sub-abrupt closure
Target lesion revascularization
Myocardial infarction
Death
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno Scheller, MD
Organizational Affiliation
University Hospital, Saarland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Wolfgang Rutsch, MD
Organizational Affiliation
Charite Hospital, Berlin
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Saarland
City
Homburg/Saar
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
Facility Name
Charite University Hospital
City
Berlin
ZIP/Postal Code
10117
Country
Germany
12. IPD Sharing Statement
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Short-Term Exposure to Lipophilic Anti-proliferative Drugs Delivered by Angiographic Contrast Media
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