Clinical Outcomes of Drug-Coated Balloons in the Treatment of Patients With Coronary De Novo Chronic Total Occlusion Lesions: A Multicenter, Randomized Controlled Trial

Background Despite significant advances in percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO), the standard drug-eluting stent (DES) implantation strategy following successful recanalization-particularly for long-segment lesions-faces challenges associated with the "full metal jacket" phenomenon. These include increased risks of in-stent restenosis (ISR) and stent thrombosis (ST), impairment of vascular physiological function, and prolonged requirements for dual antiplatelet therapy (DAPT). Drug-coated balloon (DCB), as a "leave nothing behind" interventional technique, has demonstrated efficacy in treating DES-ISR and small vessel disease, offering a potential alternative for CTO treatment. However, its application in de novo CTO lesions remains supported by limited high-level evidence from large-scale randomized controlled trials (RCTs).

Objective This study aims to compare the long-term efficacy and safety of a DCB-based treatment strategy (including DCB alone or DCB combined with provisional DES hybrid strategy when necessary) versus standard DES-only strategy in patients with successfully recanalized native CTO lesions. The primary objective is to evaluate whether the DCB strategy is non-inferior to the DES-only strategy regarding in-segment late lumen loss (LLL) at 9 months post-procedure. Secondary objectives include comparisons of clinical endpoints (such as target lesion failure [TLF], cardiac death, myocardial infarction, and repeat revascularization), angiographic restenosis rates, patient-reported outcomes (angina, quality of life), intravascular imaging parameters, safety profiles, and cost-effectiveness between the two groups.

Methods This is a prospective, multicenter, randomized, open-label, active-controlled non-inferiority clinical trial. We plan to enroll 200 patients with successfully recanalized native CTO (reference vessel diameter 2.25-4.0 mm), who will be randomly assigned in a 1:1 ratio to either the DCB strategy group or the DES-only strategy group. The DCB group will undergo DCB angioplasty, with provisional DES implantation (hybrid strategy) permitted in cases of flow-limiting dissection or suboptimal results. The DES group will receive standard DES implantation. All patients will receive standard post-procedural medical therapy (including at least 12 months of DAPT) and will be followed up for 36 months post-procedure. The primary endpoint of in-segment LLL at 9 months will be assessed by an independent core laboratory, blinded to group allocation, using quantitative coronary angiography (QCA). Clinical endpoint events will be adjudicated by an independent Clinical Events Committee (CEC). Statistical analysis will be primarily based on the intention-to-treat (ITT) principle.

Expected Significance This study (the DCB-CTO Study) is expected to provide the first large-scale RCT evidence directly comparing DCB strategy versus DES-only strategy for de novo CTO. The findings will furnish clinicians with important evidence-based guidance for managing this complex lesion subset, potentially optimizing interventional treatment strategies for CTO, reducing metallic implant burden, and possibly improving long-term clinical outcomes for patients.