Clinical Outcomes of Drug-Coated Balloons in the Treatment of Patients With Coronary De Novo Chronic Total Occlusion Lesions

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

The aim of this study is to evaluate the long-term efficacy and safety of drug-coated balloon (DCB) strategies, including DCB alone or hybrid strategies of DCB and drug-eluting stent (DES), compared to DES-only in patients with chronic total occlusion (CTO) after successful recanalization. Through a prospective, multicenter randomized controlled trial, we will directly compare the long-term outcomes of these two treatment strategies in CTO patients to fill the gap in existing research regarding direct comparative data between DCB and DES in CTO treatment. This study expects to provide high-quality evidence for optimizing CTO treatment, potentially improving treatment strategies in complex cases, reducing stent usage, lowering the risk of complications, and ultimately enhancing patient prognosis.

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.

Inclusion Criteria:

• Patient voluntarily participates in the study and has provided written informed consent.
• Presence of clinical indication for Percutaneous Coronary Intervention (PCI) of the Chronic Total Occlusion (CTO) (e.g., symptoms of angina pectoris or evidence of myocardial ischemia).
• Target lesion is located in a de novo coronary artery.
• Angiographically confirmed CTO (TIMI grade 0 flow), with evidence supporting an occlusion duration of ≥ 3 months.
• Successful guidewire crossing of the target CTO lesion has been achieved during the index procedure.
• After adequate vessel preparation: Distal TIMI grade 3 flow has been restored; Target lesion residual diameter stenosis is < 50% (e.g., by visual estimate or QCA as per protocol); Absence of flow-limiting dissection or other complications requiring immediate stent implantation.
• Target vessel Reference Vessel Diameter (RVD) is between 2.25 mm and 4.0 mm (inclusive, assessed by visual estimate or QCA/IVUS as per protocol).
• In the judgment of the interventional operator, the lesion is deemed suitable for treatment with both a Drug-Coated Balloon (DCB)-based strategy and a Drug-Eluting Stent (DES)-only strategy.
• Patient is able and willing to comply with the study protocol requirements, including the specified follow-up schedule.
• Female patients of childbearing potential must have a negative pregnancy test prior to enrollment and agree to use an effective method of contraception throughout the study period.

Exclusion Criteria:

• Target CTO lesion is the culprit vessel responsible for the presenting Acute Myocardial Infarction (AMI).
• Patient is in cardiogenic shock.
• Presence of severe heart failure (New York Heart Association [NYHA] Class IV) or Left Ventricular Ejection Fraction (LVEF) < 30%.
• History of stroke or Transient Ischemic Attack (TIA) within the previous 3 months.
• Known high risk of bleeding or contraindication to Dual Antiplatelet Therapy (DAPT).
• Presence of severe hepatic impairment and/or severe renal impairment (e.g., estimated Glomerular Filtration Rate [eGFR] < 30 ml/min/1.73m² or requirement for chronic dialysis).
• Known hypersensitivity or contraindication to required study medications (e.g., antiplatelet agents, contrast media), DCB/DES drug coatings, or device materials (e.g., stent alloys, polymers).
• Target lesion located in an unprotected left main coronary artery, a saphenous vein graft, or an arterial graft.
• Presence of severe lesion calcification that prevents adequate vessel expansion despite attempted lesion preparation techniques (e.g., rotational atherectomy, intravascular lithotripsy).
• Target lesion is a CTO within a previously stented segment (In-Stent Restenosis [ISR] or In-Stent Thrombosis [IST]).
• Failed attempt at CTO recanalization during the index procedure (i.e., failure to cross the lesion with a guidewire or failure to restore TIMI grade 3 flow).
• Occurrence of a complication after vessel preparation that necessitates immediate stent implantation (e.g., flow-limiting dissection, perforation requiring a covered stent).
• Concurrent enrollment in another interventional clinical trial that may interfere with the study endpoints or assessments.
• Female patient is pregnant or breastfeeding.
• Patient judged by the investigator to be unsuitable for the study for any reason, including anticipated poor compliance with the protocol.