A Prospective, Randomized Controlled Trial of Stent Graft and Drug Coated Balloon Treatment for Recurrent Cephalic Arch Stenosis in Dysfunctional Arteriovenous-venous Fistula

Study Overview
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Brief Summary
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Arteriovenous Fistula (AVF) is a surgically created circuit used for hemodialysis in patient with End Stage Renal Disease (ESRD). A functioning dialysis vascular access is critical to the delivery of life-saving hemodialysis (HD) treatment for these patients. Unfortunately, neointimal hyperplasia frequently occurs within the dialysis vascular access, resulting in stenosis, poor flow and thrombosis with loss of function. The cephalic vein forms the outflow conduit for radiocephalic (RC) and brachiocephalic (BC) AVF. At the perpendicular portion of the cephalic vein, the cephalic arch is often prone to developing hemodynamically significant stenosis. The prevalence of cephalic arch stenosis is reported to be 39% in brachiocepahlic and 2% in radiocephalic AVF. The current gold standard therapy for treatment of AVF stenosis is plain balloon angioplasty (BA). Paclitaxel coated balloon (PCB) angioplasty has also been shown recently to be superior to plain BA in the treatment of stenosis in dialysis vascular access. By releasing paclitaxel, which is an anti-proliferation drug, locally into the vessel wall during balloon contact, it will blunt the acceleration of intimal hyperplasia response, resulting in improved primary patency after angioplasty. The use of stent grafts for recurrent CAS has been demonstrated to increase patency of AVF compared to BA and bare stents. However, stent grafts are prone to edge restenosis that tend to occur within 5mm of each end of SG due to neointimal hyperplasia from the end of the stent migrating towards the center. We postulate that stent graft with PCB angioplasty of the stent edge is more effective than PCB alone in maintaining the patency of AVF with cephalic arch stenosis. Therefore, we aim to perform a randomized controlled trial to compare the 6-month unassisted patency rate of treatment of recurrent CAS with stent graft and PCB angioplasty of both stent edge versus PCB alone.

Official Title
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A Prospective, Randomized Controlled Trial of Stent Graft and Drug Coated Balloon Treatment for Recurrent Cephalic Arch Stenosis in Dysfunctional Arteriovenous-venous Fistula

Conditions
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Neointimal Hyperplasia, Dialysis Access Malfunction

Intervention / Treatment
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* Device: Paclitaxel Coated Balloon
* Device: Paclitaxel Coated Balloon and Stent Graft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 - 90 years Patients who requires balloon angioplasty for dysfunctional arteriovenous fistula, can be de novo lesions or recurrent CAS stenosis within six months of interventions. Suitability will be determined with a baseline ultrasound assessment. Matured AVF, defined as being in use for at least 1 month prior to angioplasty Successful angioplasty of the underlying stenosis, defined as less than 30% residual stenosis on Digital Subtraction Angiography (DSA). Exclusion Criteria: Patient unable to provide informed consent Thrombosed or partially thrombosed AVF Immature AVF Insignificant CAS defined as <50% stenosis and no clinical indicator such as high V pressure. Presence of central vein stenosis with more than 30% residual stenosis post-angioplasty Patient who had underwent stent placement within the CAS previously Patients who are allergic to both aspirin or clopidogrel Patient who are currently enrolled in other drug eluting balloon trials Sepsis or active infection Recent intracranial bleed or gastrointestinal bleed within the past 12 months. Allergy to iodinated contrast media, heparin or paclitaxel Pregnancy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PCB Only<br>Cephalic arch stenosis is first treated with conventional plain balloon angioplasty. Once treated adequately (<30% residual stenosis), CAS will be treated with PCB angioplasty. | Device: Paclitaxel Coated Balloon<br>* CAS treated with PCB only<br>|
| Experimental: Stent Graft and PCB angioplasty of stent edges<br>CAS is first treated with conventional plain balloon angioplasty. Once treated adequately (<30% residual stenosis), CAS will be treated with PCB first to avoid geographical miss. After which, stent graft will be deployed. Length of PCB shall be long enough to cover stent edges. | Device: Paclitaxel Coated Balloon and Stent Graft<br>* CAS treated with PCB first before deployment of stent graft<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency of Target Lesion (Cepahlic Arch) | Freedom from any re-intervention at target lesion that is clinically driven or indicated on surveillance scan | 6-months post-op | 
| Primary Patency of Access Circuit | Percentage of patients who do not need to undergo another re-intervention at the dialysis access circuit | 6-months post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency of Target Lesion | Percentage of patients who do not need to undergo another re-intervention at the target lesion | 3 and 12 months post-op | 
| Primary Patency of Access Circuit | Freedom from any re-intervention that is clinically driven or indicated on surveillance scan | 3 and 12 months post-op | 
| Assisted Primary Patency of Target Lesion | Percentage of patients who do not need to undergo another thrombolysis or thrombectomy at target lesion. | 3 and 12 months post-op | 
| Assisted Primary Patency of Access Circuit | Percentage of patients who do not need to undergo another thrombolysis or thrombectomy at dialysis access circuit | 3 and 12 months post-op | 
| Secondary Patency | Percentage of patients who will not need creation of a new AVF or an alternative dialysis access site. | 3 and 12 months post-op | 
| Time taken to next intervention |  | 12-months post-op | 
| Number of repeat interventions to target lesion |  | 6 and 12 months post-op | 
| Number of repeat interventions to maintain access circuit |  | 6 and 12 months post-op | 
| Rate of late lumen loss of the cephalic arch, proximal and distal stent edge |  | 12 months post-op | 
| Complication Rate |  | 1, 3, 6 and 12 months post-op |