Prospective Randomized Trial Comparing DEB Versus Conventional PTA for the Treatment of Hemodialysis AVF or AVG Stenoses (DEBAPTA)

• Restenosis rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Restenosis rate is defined as the incidence of stenosis ≥50% of the diameter of the reference vessel segment.
• Primary patency [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Primary patency is defined as the interval from balloon angioplasty until the next access thrombosis or repeated intervention to maintain access function, or until access abandonment if no interval intervention. It ends with treatment of a lesion anywhere within the access circuit, from the arterial inflow to the superior vena cava-right atrial junction.
• Primary assisted patency [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Primary assisted patency is defined as the interval from balloon angioplasty until access thrombosis or a surgical intervention that excludes the treated lesion from the access circuit. Examples include percutaneous treatments of either restenosis/occlusion of the previously treated lesion or a new arterial or venous outflow stenosis/occlusion (excluding access thrombosis). It ends with percutaneous thrombolysis/thrombectomy or simple surgical thrombectomy.
• Secondary patency [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Secondary patency is defined as the interval after balloon angioplasty until the access is surgically declotted, revised or abandoned because of inability to treat the original lesion, choice of surgeon, transplant, loss to follow-up, etc. Examples include thrombolysis and percutaneous thrombectomy, as well as multiple repetitive treatments.
• Anatomic success [ Time Frame: Immediate post procedure ] [ Designated as safety issue: No ]
  Anatomic success is defined as <30% residual stenosis diameter measured immediately after angioplasty.
• Clinical success [ Time Frame: Immediate post procedure ] [ Designated as safety issue: No ]
  Clinical success is defined as an improvement from baseline in the clinical or hemodynamic parameter (e.g., blood flow, venous pressures) that was the initial indicator of fistula/ graft dysfunction.
• Procedural success [ Time Frame: Immediate post procedure ] [ Designated as safety issue: No ]
  Procedural success is defined as the combination of anatomic success and clinical success.

A prospective randomized trial comparing the efficacy of drug eluting balloon angioplasty versus conventional percutaneous transluminal angioplasty balloon for the treatment of hemodialysis arterio-venous fistula or arterio-venous graft stenoses in reducing late luminal loss and restenosis rates, while prolonging primary and secondary patencies.

Introduction:

Neointimal hyperplasia is the main cause of hemodialysis access [arterio-venous fistula (AVF) or graft (AVG)] dysfunction and thrombosis. Although endovascular techniques like percutaneous transluminal angioplasty (PTA), catheter directed thrombolysis, mechanical thrombectomy or bare metal stenting, may salvage the access, long term patency remains dismal due to recurrent stenosis from neointimal hyperplasia.

Drug Eluting Balloon (DEB) is effective in inhibiting neointimal hyperplasia for treatment of coronary in-stent restenosis since 2006 and more recently in femoropopliteal arteries, reducing restenosis rates and prolonging patency.

Specific Aim:

To determine the efficacy of DEB in reducing restenosis rates and prolonging the patency of AVFs/AVGs compared to PTA.

Hypothesis:

DEB is superior to PTA in reducing late luminal loss and restenosis rates, while prolonging primary and secondary patencies.

Methodology:

Prospective, randomized clinical trial with study population comprising of patients with dysfunctional AVFs/AVGs due to underlying stenoses. The patients will be randomized to receive either DEB or PTA.

The 6-month late luminal loss will be primary endpoint. The secondary endpoints of restenosis rate, primary and secondary patencies, will also be determined.

Major Clinical Significance:

Hemodialysis access failures constitute significant morbidity and costs to patient and healthcare system. Maintaining access patency consumes significant resources and constitutes a significant portion of the work of vascular surgeons, nephrologists and interventional radiologists.

Any strategy that reduces access failure or prolonging access lifespan will be beneficial. If DEB is proven to be superior to PTA, there will be a paradigm shift in management of hemodialysis access failures from restenosis - similar to how DEB has changed practice in managing coronary artery in-stent restenosis.

• Stenosis of Arteriovenous Dialysis Fistula
• Arteriovenous Graft Stenosis

• Device: Conventional PTA
  Use of conventional balloon for angioplasty only
  Other Name: REEF angioplasty balloon (Manufacturer Medtronic)
• Device: Drug Eluting Balloon (DEB)
  Use of DEB after conventional balloon angioplasty
  Other Name: IN.PACT ADMIRAL Paclitaxel-eluting Balloon (Medtronic)

• Active Comparator: Conventional PTA only

  Treatment Arm 1- Conventional PTA only

  The conventional balloon is used and the diameter of the balloon should be the same or oversized by 1mm the diameter of the reference vessel.

  An inflation device with a pressure gauge is used to inflate up to manufacturers' stated burst pressure. The duration of balloon inflation will be 2 minutes.

  At the end of the first angioplasty, an AVFistulogram/AVGraftogram will be obtained to document results. If there is residual stenosis of >30%, a repeat angioplasty using the same balloon or another appropriately oversized balloon by 1mm will be used for an additional 2 minutes. A final angiogram will be obtained for documentation.

  Intervention: Device: Conventional PTA
• Experimental: Drug Eluting Balloon (DEB)

  Treatment arm 2 - Conventional Balloon with DEB

  A Conventional balloon is used to pre-dilate the target lesion. The DEB of a similar diameter to the conventional balloon used is then inflated across the stenosis. An inflation device with a pressure gauge is used to inflate up to manufacturers' stated burst pressure. The duration of balloon inflation will be 1 minute. A final angiogram will be obtained for documentation. The drug coated on the DEB is Paclitaxel.

  Intervention: Device: Drug Eluting Balloon (DEB)

Inclusion Criteria:

1. Upper limb or groin AVF/AVG
2. The AVF/AVG is > 3 months old.
3. Native vessel measures between 4 to 7 mm diameter (corresponding to the sizes of available DEBs).
4. The fistula or graft must not be thrombosed.
5. Able to cross with guide wire
6. Platelet count >50,000/l (platelet infusion if <100,000/l)
7. PT/PTT not more than 3 seconds above normal (FFP infusion for abnormal PT/PTT)

Exclusion Criteria:

1. Uncorrectable coagulopathy (despite transfusion) or hypercoagulable state.
2. Evidence of systemic infection or a local infection associated with the fistula or graft.
3. The patient is < 21 years of age.
4. The patient is pregnant.
5. Patient is enrolled in another investigational study
6. Patient has comorbid conditions that may limit their ability to comply with the follow-up requirement.
7. Life expectancy < 6 months