Paclitaxel-coated Balloon Angioplasty Versus Standard Angioplasty for the Treatment of Stenosis of Arteriovenous Fistula

Study Overview
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Brief Summary
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The primary objective of this double-blind study is to compare the frequency of primary patency at 6 months in patients with stenosis of arteriovenous fistula (AVF) treated either by conventional angioplasty + angioplasty with balloon impregnated with paclitaxel or by conventional angioplasty + angioplasty with placebo balloon (balloon not impregnated with paclitaxel). The other objectives of the study are: To compare the frequency of primary patency at 3 months and 12 months. To compare the rate of restenosis > 50% at the site of angioplasty at 3, 6 and 12 months. To compare, at 3, 6 and 12 months, the proportion of patients with arteriovenous fistula deteriorating back to preoperative flow rate (within 20% of preoperative flow rate). To compare, at 3, 6 and 12 months, the proportion of AVF with a flow rate < 500 ml / min. To compare, at 3, 6 and 12 months, the cumulative rate of thrombosis. To compare, at 3, 6 and 12 months, the medical costs related to direct medical care, initial treatments, monitoring, diagnosis and treatments of complications.

Detailed Description
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Experimental design: prospective randomized, double blind, multicenter controlled study, with 2 experimental arms. 12 centers will participate in France, targeting to enrol 150 patients in total. Each patient will undergo angiography at the beginning of the intervention in order to confirm the presence of only one stenosis, to assess the degree of stenosis and to evaluate the vascular diameter. All patients will first undergo angioplasty using standard balloons. thereafter, depending on randomization arm, an additional angioplasty will be performed during 1 minute with a paclitaxel impregnated balloon (active arm) or with a placebo balloon (placebo arm). The duration of inclusion is planned for 18 months. Each patient will have a 12-month follow-up.

Official Title
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Paclitaxel-coated Balloon Angioplasty Versus Standard Angioplasty for the Treatment of Stenosis of Arteriovenous Fistula

Conditions
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Angioplasty, Stenosis of Arteriovenous Fistula

Intervention / Treatment
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* Combination Product: Additional angioplasty with paclitaxel-coated balloon
* Combination Product: Additional angioplasty with placebo balloon
* Procedure: Conventional angioplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, man or woman. Chronic Hemodialysis. Native autologous arteriovenous fistula (AVF). AVF used at least once for hemodialysis. Preoperative flow measurement of AVF performed by Doppler. Length of the stenosis <120 mm. Outer diameter of the target vein <12mm. Hemodynamically significant Stenosis on AV fistula, defined according to international recommendations with the following two criteria: stenosis> 50% by Doppler or angiography, presenting at least one of the following : increased venous pressure during dialysis (venous pressure > 150 mmHg when blood flow measured at 200-225 ml / min, or venous pressure > 230 mmHg when blood flow measured at 400 ml / min); disappearance of thrill of AV fistula; increasing hemostasis time at the end of dialysis (> 20 minutes or increase by >=50% from usual hemostasis time); recirculation rate > 20%; flow of AVF < 500 ml / min responsible for a reduction of the flow of the dialysis circuit. Only one stenosis with significant impact hemodynamically. Signed informed consent. Patient has a health insurance. Exclusion Criteria: Pregnant or breastfeeding women. Severe allergy to iodinated contrast agents, or to heparin, or to paclitaxel. Anastomotic stenosis involving the afferent artery. Multiple hemodynamically significant stenoses. Hemodynamically significant central venous stenosis. Stent already in place in treated vascular site. Diameter of the vein immediately upstream of stenosis greater than the maximum diameter of active balloon. AVF in lower limb. Coagulation disorder (outside of VKA use). Active infection. Inability to comply with the protocol requirements. Life expectancy less than 1 year due to progressive disease (neoplasia, severe organ failure). Follow-up expected to be difficult. Patient under guardianship.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Conventional angioplasty + paclitaxel-coated balloon<br>Treatment of stenosis of AVF by conventional angioplasty + 1 minute additional angioplasty with paclitaxel-coated balloon | Combination Product: Additional angioplasty with paclitaxel-coated balloon<br>* Additional angioplasty with paclitaxel-coated balloon after conventional angioplasty<br>* Other names: Lutonix® 035 balloon;Procedure: Conventional angioplasty<br> <br> |
| Placebo Comparator: Conventional angioplasty + placebo balloon<br>Treatment of stenosis of AVF by conventional angioplasty + 1 minute additional angioplasty with placebo balloon. | Combination Product: Additional angioplasty with placebo balloon<br>* Additional angioplasty with placebo balloon after conventional angioplasty<br>* Other names: ClearPAC Omega® balloon;Procedure: Conventional angioplasty<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated incidence of loss of primary patency of AVF | Double-blind comparison of cumulated incidence of primary patency at 6 months after treatment of stenosis of AVF by conventional angioplasty + additional angioplasty. Cumulated incidence of primary patency loss of AVF at 6 months post procedure. | At 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulated incidence of primary patency loss of the target lesion | Comparison between arms of cumulated incidence of primary patency loss of treated lesion at 3 and 12 months after treatment of stenosis. By cumulated incidence with no need for target lesion revascularization. | At 3 months and 12 months | 
| Cumulated incidence of restenosis > 50% at the site of angioplasty | Comparison between the arms of cumulated incidence of restenosis > 50% at the site of angioplasty of treated lesion of AVF, by cumulated incidence with at least one restenosis at angioplasty site at 3, 6 and 12 months. | At 3, 6 and 12 months | 
| Cumulated incidence of deteriorating flow rate | Cumulated incidence at 3, 6 and 12 months of deteriorating back to preoperative flow rate of AVF: defined by the difference of flow rate < 20% between preoperative measurement and follow-up measurement. Incidence of back to preoperative flow rate will be cumulated. | At 3, 6 and 12 months | 
| Cumulated incidence of patients with a flow rate < 500 ml / min | Comparison between the arms of cumulated incidence with a flow rate < 500 ml/min after treatments of stenosis. | At 3, 6 and 12 months | 
| Cumulative rate of thrombosis | Comparison between the arms at 3, 6 and 12 months cumulative rate of thrombosis, by the proportion of thrombosis of AVF, number of restenosis and number of thrombosis. | At 3, 6 and 12 months | 
| Time period before event's appearance | Comparison between the arms time periods before the events' appearance: restenosis at the same site, stenosis at another site, thrombosis of AVF, death. | At 12 months | 
| Cumulated incidence of adverse event (AE) | Comparison between the arms post procedure AE, by cumulated incidences of AE in 12 months post procedure. | At 12 months | 
| Medical costs | Comparison between the arms at 3, 6 and 12 months the costs of treatments of AVF, by direct medical care, initial treatments, monitoring, diagnosis and treatment of complications. | At 3, 6 and 12 months | 
| Cumulative incidence of cardiovascular serious adverse event (SAE) | Comparison between the arms at 12 months the cumulative incidence of cardiovascular SAE. | At 12 months | 
| Cumulative incidence of death | Comparison between the arms at 12 months the cumulative incidence of death. | At 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stenosis of arteriovenous fistula, Angioplasty, Paclitaxel-Coated Balloon Angioplasty