Sirolimus Drug-coated Balloon Versus Stent Graft for Thrombosed Arteriovenous Graft (SUSTAIN)

Arteriovenous graft (AVG) is a surgically created vascular access used for hemodialysis (HD). Neointimal hyperplasia frequently occurs within AVG, resulting in flow-limiting stenosis and thrombosis. The primary patency rates of AVGs after creation were 58% at 6 months and 33% at 18 months. Hence, vascular access failure has been a common reason for hospitalization among HD patients. The culprit lesion in AVG thrombosis is usually the graft-vein (GV) junction stenosis. Histopathology examination of thrombosed AVG demonstrated maximal neointimal hyperplasia at the GV junction. Thrombolysis combined with percutaneous transluminal angioplasty (PTA) of underlying stenosis has been the standard of care to restore the function of thrombosed AVGs. Despite its widespread availability and minimally invasive nature, the mid- and long-term patency of PTA for thrombosed AVG is far from satisfactory. The reported access circuit primary patency (ACPP) rate of thrombosed AVG following thrombolysis combined with PTA alone was only 23.5% at 6-month. This is because PTA is purely a mechanical intervention that does not address the underlying biological process of neointimal hyperplasia.

Stent graft is a type of vascular stent with expanded polytetrafluoroethylene (ePTFE) coating. It provides mechanical scaffolding that keeps vascular lumen open while the ePTFE coating limits neointimal hyperplasia. The therapeutic efficacy of stent graft in the treatment of graft vein junction stenosis has been convincingly demonstrated in several randomized controlled trials (RCTs). For thrombosed AVG, the reported access circuit primary patency rates at 6-month following stenting were 34% compared to 21.8% with PTA alone. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guideline for Vascular Access: 2019 Update therefore suggests the use of stent-grafts in preference to PTA alone to treat clinically significant GV junction stenosis in AVG for a better 6-month postintervention outcome. Despite its superiority compared to PTA in maintaining the short- and long-term patency of thrombosed AVG, stent graft is expensive and may not be suitable for all patients as it could impede future surgical revision or creation of a secondary vascular access in the ipsilateral arm. Furthermore, the deployment of stent graft is technically challenging and requires refined interventional skills in experience hands to ensure accurate landing and prevent migration.

Drug-coated balloon (DCB) is a balloon catheter that is coated with an anti-proliferative drug. The drug is delivered directly to the vessel wall upon balloon inflation to prevent neointimal hyperplasia and restenosis. The efficacy of DCB have been shown in several randomized controlled trials. Liao et al demonstrated that angioplasty with DCB resulted in a modest improvement in primary patency of AVG with GV junction stenosis. We conducted a prior pilot study to examine the feasibility of Sirolimus DCB angioplasty at the GV junction following successful PTA for thrombosed AVGs. Our study demonstrated an ACPP of 55% at 6 months. This finding could imply that Sirolimus DCB can be an alternative option to stent graft deployment which is the recommended treatment. DCBs are cheaper and will not impede future secondary vascular access creation. Furthermore, DCB angioplasty is similar to PTA with plain balloon procedurally, thus it is not as technically challenging as stent graft deployment and does not require highly skilled operators.

The investigators aim to perform a single-centre 2-arm parallel randomized non-inferiority trial to compare the 6-month post-intervention access circuit primary patency (ACPP) of sirolimus DCB versus stent graft in the management of thrombosed AVG.

RECRUITMENT Patients who are admitted to the hospital for thrombosed AVG will be screened and offered enrollment if they meet the inclusion criteria. Patients will be consented if they fulfill the preliminary eligibility criteria and agree to participate in the study. Patients who have successful thrombectomy of the AVG is entered to the trial and randomized to receive either sirolimus DCB or stent graft. Patients who are unsuitable for the trial will be treated in the according to hospital standard protocol.