Use of Implanting the Biotronik Passeo-18 Lux Drug Coated Balloon to Treat Failing Haemodialysis Arteriovenous Fistulas and Grafts.

Study Overview
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Brief Summary
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The most common problem with haemodialysis arteriovenous fistulas (AVF) and arterio-venous grafts (AVG) is stenosis, which can lead to inadequate dialysis, and eventual access thrombosis. Conventional plain old balloon angioplasty is associate with high recurrence rates of stenosis and repeated interventions. The advent of successful drug-eluting technology in the treatment of the coronary vascular bed and subsequent positive accumulating evidence in the peripheral arterial circulation has prompted the use of drug coated balloons (DCB) in the access fistula circuit for venous stenosis and in-stent restenosis. Recent studies suggest that DCBs may significantly reduce re-intervention rates on native and recurrent lesions. The restenosis process is in part or in whole the result of neo-intimal hyperplasia (NIH) and NIH is considered the main culprit in access circuit target lesion stenosis. NIH is the blood vessel's healing response to the barotrauma from the angioplasty process. A critical component of NIH is the cellular proliferative stage with mononuclear leucocytes identified as the primary inflammatory cell type involved. The rationale for drug elution is to block the NIH response with an anti-metabolite such as paclitaxel. It is important to emphasize that the role of drug elution in the treatment of vascular stenosis is not to obtain a good haemodynamic and luminal result but to preserve a good result obtained during POBA from later restenosis due to NIH and minimise reinterventions and readmissions to hospital for what is a frail population of patients. A meta-analysis performed by Khawaja et al. seemed to suggest that DCBs conferred some benefit in terms of improving target lesion primary patency (TLPP) in AVFs. An updated meta-analysis performed by our own institution recently showed that DCB appears to be a better and safe alternative to conventional balloon angioplasty (CBA) in treating patients with HD stenosis based on 6- and 12-months primary patency and increased intervention free period. The Passeo-18 Lux (Biotronik Asia Pacific Pte Ltd (Singapore)) drug-coated balloon (DCB) is packaged with a low dose of paclitaxel. Recent studies have shown that low dose coating of paclitaxel with this DCB is useful for preventing restenosis, decrease lumen loss and target lesion revascularization in the peripheral vasculature6 but has not been tested in the dialysis access circuit.

Official Title
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Use of Implanting the Biotronik Passeo-18 Lux Drug Coated Balloon to Treat Failing Hemodialysis Arteriovenous Fistulas and Grafts

Conditions
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Arterio-venous Fistula, Dialysis Access Malfunction, Hemodialysis Access Failure, Arteriovenous Graft Stenosis

Intervention / Treatment
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* Device: Passeo-18 Lux


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged ≥21 years and ≤90 years Native AVF was created more than 2 months prior to the index procedure and had undergone 10 or more hemodialysis sessions utilizing 2 needles Target lesion location had to be located between the anastomosis to the axillary-subclavian vein junction, as defined by insertion of the cephalic vein. On initial fistulogram, target lesion stenosis had to be >50% on angiographic assessment and in keeping with the clinical indicator for intervention Stenosis had to be < 10cm in length to allow for potential treatment with one PCB (length 12 cm) only Stenosis had to be initially treated successfully with a high-pressure plain balloon prior to PCB treatment as defined by: No clinically significant dissection No extravasation requiring treatment/stenting Residual stenosis ≤20% by angiographic measurement Ability to completely efface the lesion waist using the pre-dilation balloon No more than one additional (nontarget) lesions in the access circuit that had to be also successfully treated (≤30% residual stenosis) before drug elution. Separate lesion was defined by at least 3 cm in distance from the target lesion. Reference vessel diameter 4mm - 8mm Exclusion Criteria: Women who were pregnant, lactating, or planning on becoming pregnant during the study Subject had more than two lesions in the access circuit Subject had a secondary non-target lesion that could not be successfully treated Sepsis or active infection Asymptomatic target lesions A thrombosed access or an access with thrombosis treated ≤30 days prior to the index procedure Surgical revision of the access site performed, planned or expected ≤ 3 months before or after the index procedure Patients who were taking immunosuppressive therapy or are routinely taking ≥ 15 mg of prednisone per day; Currently participating in an another investigational drug, biologic, or device study involving sirolimus or paclitaxel Contraindication to aspirin or clopidogrel usage Mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, or language barrier such that the subject is unable to give informed consent Uncooperative attitude or potential for non-compliance with the requirements of the protocol making study participation impractical Where final angioplasty treatment requires a stent or drug eluting balloon > 8mm in diameter Metastatic cancer or terminal medical condition Blood coagulation disorders Limited life expectancy (< 12 months) Allergy or other known contraindication to iodinated media contrast, heparin or paclitaxel

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AVG/AVF Treated with Passeo-18 Lux<br>Patients with failing dialysis access, treated lesions located between the anastomosis to the axillary-subclavian vein junction. | Device: Passeo-18 Lux<br>* Patients with significant inflow or outflow stenosis between the anastomosis to the axillary-subclavian vein junction, as defined by the insertion of the cephalic vein, who had undergone fistuloplasty with Passeo-18 Lux<br>* Other names: Biotronik;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-month Target Lesion Primary Patency | Patency with no re-intervention to the area 5mm proximal to, within, and 5mm distal to, the index treatment segment. TLPP ends when any of the following occur: 1) clinically driven re-intervention to the treatment segment 2) thrombotic occlusions that includes the treatment segment 3) surgical intervention that excludes the treatment segment from the access circuit 4) abandonment of the AVF/AVG due to an inability to treat the treatment segment | 6-month post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Patency | A duration of time measuring intra-access patency that starts from the date of angioplasty with Passeo-18 Lux DCB to the date of one of the following events: thrombosis, or any intervention to facilitate, maintain or re-establish patency (e.g. angioplasty) | 12 months post-op | 
| Primary assisted patency | Interval date of angioplasty with Passeo-18 Lux DCB until thrombosis | 12 months post-op | 
| Secondary Patency | A duration of time measuring intra-access patency that starts from the date of angioplasty with Passeo-18 Lux DCB to the date of vascular access abandonment | 12 months post-op | 
| Number of reinterventions |  | 12 months post-op | 
| Adverse Events | Intraoperative/perioperative complications, infections, revision surgeries required | 12 months post-op |