Drug Coated Balloons for Prevention of Restenosis

Study Overview
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Brief Summary
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The study will be performed as a randomized, double blind trial (in respect of the primary end point) with treatment of the stenotic lesion using uncoated PTA-catheters as control group. 114 patients will be included in the trial at about 5 study centers. Follow-up includes control angiography after 6 and 18 months and clinical follow-up examinations up to 18 months. Primary objective: Efficacy of paclitaxel coated PTA balloons in inhibiting restenosis of below the knee arteries (late lumen loss) Secondary objective: Various angiographic and clinical efficacy measures, safety and tolerance of pacli-taxel coated PTA balloons in inhibiting restenosis of below the knee arteries Descriptive statistics, comparison by t-test, chi-square test for binary events 10.1 Descriptive statistics As far as applicable descriptive statistics will be applied to data and will be referring to individual changes versus baseline (predilatation or immediately postdilatation). The groups will be compared to each other testing the statistical significance of differences (p ≤ 0.05). Con-tinuous data will be expressed as mean ± standard deviation. Categorical variables will be compared using the chi-squared test, and continuous variables will be compared using Student's t test or ANOVA analysis. In addition to the assessment of the primary endpoint and the secondary endpoints a multi-variate analysis to investigate the influence of risk factors on the interventional outcome (interventional success, early restenosis/occlusion, LLL, stent integrity) and clinical outcomes will be performed. For this analysis the following factors will be considered: age, diabetes, neurological status (only Rutherford 5), lesion length, grade of dissection and calcification, reststenosis, number of run-off vessels, stent administration in the index lesion(s). 10.2 Estimated number of patients The primary endpoint of the study is late lumen loss (LLL) at 6 months evaluated by quantitative angiography. Because no data according this endpoint are available for both the control group and the group which will be treated with the paclitaxel coated balloon an assumption according the LLL at 6 months was made according the expectations of the principle investigator. An estimate for LLL as % of MLD in the control group is 50% and in the drug coated balloon group 30 %. The standard deviation is calculated to be 30% of LLL. A sample size of 37 patients in each group will allow the detection of a statistically significant difference (p<0.05) with 80% power. Based on the Below study which enrolled patients with comparable arterial lesions in Tuebingen and the data of the Basil study, it is estimated that 35% of the patients who will be enrolled in the study will not be available for follow-up investigations in order to calculate the MLD. In order to meet a statistical endpoint a total of 114 patients will be enrolled.

Official Title
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Paclitaxel Coated Balloons for Prevention of Restenosis in Small Arteries Below the Knee Compared to Angioplasty Using Uncoated Balloons

Conditions
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Atherosclerosis, Restenosis, Limb Ishemia

Intervention / Treatment
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* Device: Balloon angioplasty (uncoated conventional balloon)
* Device: Balloon angioplasty (conventional but coated with 3 µg/mm2 paclitaxel)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 95 years, peripheral vascular disease, Rutherford stage 3-5, diameter stenosis ≥ 70 %, ≥ 15 -150 mm length, up to 2 vessels to be treated Exclusion Criteria: Disease associated with life-expectancy less than 18 months Acute thrombus or aneurysm in the index limb/ vessel Doubts in the willingness or capability of the patient to allow follow up examination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>Normal balloon for balloon angioplasty (Submarine, Ampherion Deep by Invatec) | Device: Balloon angioplasty (uncoated conventional balloon)<br>* endovascular therapy<br>|
| Active Comparator: 2<br>Paclitaxel coated balloon (same balloon like in the control group, but coated with 3 µg/mm2 Paclitaxel) | Device: Balloon angioplasty (conventional but coated with 3 µg/mm2 paclitaxel)<br>* endovascular therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint: Late lumen loss (LLL) of the target lesion after 6 months (assessed by DSA) |  | after 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interventional success rate (defined as reststenosis less than 50%) |  | up to 18 months | 
| Restenosis rate at 6 and 18 months (restenosis rate is defined as a diameter stenosis of ≥ 50% of reference diameter |  | up to 18 months | 
| Minimum lumen diameter (MLD) at 6 months |  | up to 18 months | 
| Target lesion revascularization recorded at 6, 12 and 18 months; target lesion revascularization is defined as any reintervention or artery bypass graft surgery involving the target lesion. |  | up to 18 months | 
| Target vessel revascularization recorded at 6, 12 and 18 months |  | up to 18 months | 
| Target limb revascularization recorded at 6, 12 and 18 months |  | up to 18 months | 
| Improvement of clinical stage at 6, 12 and 18 months |  | up to 18 months | 
| Change in ABI compared to pretreatment if vessels are compressible |  | up to 18 months | 
| Hospitalization (extra days due to complications of the index procedure) and hospitalization between the follow-up visits due to the index leg |  | up to 18 months | 
| Major amputations at the index limb |  | up to 18 months | 
| Mortality |  | up to 18 months | 
| LLL of stented segments at 6 months comparing the uncoated and the coated bal-loon group. |  | up to 18 months | 
| Subgroup analysis; primary endpoint and TLR |  | up to 18 months | 
| LLL, MLD and restenosis rate at 18 month follow-up determined by angiography |  | up to 18 months | 
| Subgroup analysis neuropathy and no neuropathy according to clinical improve-ment in patients classified Rutherford 5 |  | up to 18 months | 
| Clinical benefit patients Rutherford 3 vs. Rutherford 4 and 5 |  | up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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local drug delivery, balloon angioplasty, safety and tolerance of paclitaxel coated PTA balloons, in inhibiting restenosis of below the knee arteries, Efficacy of paclitaxel coated PTA balloons, in inhibiting restenosis of below the knee arteries (late lumen loss)