Head-to-head comparison of sirolimus- versus paclitaxel-coated balloon angioplasty in the femoropopliteal artery: study protocol for the randomized controlled SIRONA trial

BACKGROUND: Endovascular revascularization has established as the first-line therapy of femoropopliteal artery disease. Paclitaxel-coated balloon angioplasty proved to be superior to plain old balloon angioplasty (POBA) regarding prevention of restenosis and need for recurrent revascularization. Over the past years, paclitaxel was the only active drug to inhibit neointimal proliferation which could be processed to an appropriate balloon coating. The purpose of this study is to assess whether efficacy and safety of sirolimus-coated balloon angioplasty is noninferior to paclitaxel-coated balloon angioplasty. METHODS: This randomized controlled, single-blinded, multicentre, investigator-initiated noninferiority trial aims to enrol a total of 478 participants with symptomatic femoropopliteal artery disease of Rutherford category 2 to 4 due to de novo stenosis or restenosis. After pre-dilation, participants will be allocated in a 1:1 ratio to either sirolimus- or paclitaxel-coated balloon angioplasty. Post-dilation with the drug-coated balloon (DCB) used or standard balloon is mandatory in case ≥ 50%, and optional in case of ≥ 30% residual diameter stenosis. Bailout stenting with bare-metal nitinol stents should be conducted in case of flow-limiting dissection. Primary noninferiority endpoints are primary patency and the composite of all-cause mortality, major target limb amputation, and clinically driven target lesion revascularization at 12 months. Secondary outcomes are clinical and hemodynamic improvement, change in health-related quality of life, and safety throughout 60 months. DISCUSSION: Although concerns about long-term safety of paclitaxel-coated devices were not confirmed by recent patient-level data analyses, conflicting evidence contributed to a loss of confidence among patients and physicians. Therefore, sirolimus, known for a broader therapeutic range than paclitaxel, may serve as a welcome alternative. This will be justified if noninferiority of sirolimus-coated balloon angioplasty against the current standard of paclitaxel-coated balloon angioplasty can be demonstrated. TRIAL REGISTRATION: ClinicalTrials.govNCT04475783. Registered on 17 July 2020 EUDAMED No. CIV-20-11-035172, DRKS00022452