CAGE-FREE III: Paclitaxel-Coated Balloon Versus Zotarolimus-Eluting Stent for Treatment of De Novo Coronary Artery Lesions

Sponsor

Xijing Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05209412

Collaborator

(none)

370

Enrollment

Location

Arms

Anticipated Duration (Months)

10.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Coronary restenosis has been one of the main reasons affecting the prognosis of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). With drug-eluting stents (DES), which elutes an antiproliferative drug to the vessel wall and reduces the restenosis rate; however, the incidence of restenosis is still about 10%. The late stent thrombosis and restenosis, with a hazard of nearly 2% per year after implantation, remained a concern and motivated the development of drug-coated balloons (DCB).

DCB angioplasty has the following advantages compared with DES implantation: Firstly, the drug in DCB is uniformly distributed and released; whereas the drug release of DES via stent platform is uneven -85% of the vascular wall is not covered by the stent strut. Secondly, there is no alloy in the vessel after DCB angioplasty, while the coronary stent platform and polymer might cause temporal or persistent inflammatory response leading to intimal hyperplasia. Finally, there is no metal cage restraining vessel motion after DCB, the physiological function of coronary arteries would be maintained.

Studies with the strategy of DCB angioplasty with bailout stenting have demonstrated safety and efficacy for the small-vessel disease. The application of DCB in large vessels with de novo lesions is still to be investigated. The DEBUT study showed that in high bleeding risk patients aimed using only 1-month DAPT, DCB was superior to BMS in terms of MACE [MACE (cardiovascular mortality, nonfatal myocardial infarction or revascularization of ischemia-reperfusion target lesions)] at 9-month follow-up.

However, there is still a lack of evidence comparing the DCB versus DES in large vessels with de novo lesions. The current study aims to investigate if in patients undergoing PCI for de novo stenoses in large vessels, DCB is non-inferior to DES.

Condition or Disease	Intervention/Treatment	Phase
De Novo Stenosis Coronary Artery Disease Percutaneous Coronary Intervention	Device: Lepu Paclitaxel coated balloon Device: Resolute Integrity Zotarolimus eluting stents Drug: Aspirin Drug: Ticagrelor Drug: Clopidogrel	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

370 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Paclitaxel-Coated Balloon Versus Zotarolimus-Eluting Stent for Treatment of De Novo Coronary Artery Lesions: an Open-label, Multicenter, Randomized, Non-inferiority Trial

Actual Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug-coated balloon Lepu Paclitaxel coated balloon will be used	Device: Lepu Paclitaxel coated balloon Paclitaxel is the pharmacologically active substance for anti-neointima. The active drug coating is located on the surface of the balloon, which contains 1.5 μg Paclitaxel per 1 mm2. Drug: Aspirin Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI. Drug: Ticagrelor Ticagrelor is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI. Drug: Clopidogrel Clopidogrel is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI when Ticagrelor is unfeasible or contradicted.
Active Comparator: Drug-eluting stent Resolute Integrity Zotarolimus eluting stents will be used	Device: Resolute Integrity Zotarolimus eluting stents The device consists of a balloon-expandable intracoronary drug-eluting stent pre-mounted on the MicroTrac Rapid Exchange stent delivery system. Drug eluting stent is composed of metal stent, primer and drug coating. The Stent is manufactured from a cobalt alloy (MP35N). The strut thickness is 88.9 μm and the length elements is 0.9 mm. The drug coating consists of the zotarolimus and BioLinx polymer (C10/C19/PVP) system. A coating of polymers loaded with zotarolimus in a formulation applied to the entire surface of the stent at a dose of approximately 1.6 µg/mm2 which results in a maximum nominal drug content of 380 µg on the largest stent (4.0 x 38 mm). Drug: Aspirin Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI. Drug: Ticagrelor Ticagrelor is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI. Drug: Clopidogrel Clopidogrel is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI when Ticagrelor is unfeasible or contradicted.

Arm

Intervention/Treatment

Experimental: Drug-coated balloon

Lepu Paclitaxel coated balloon will be used

Device: Lepu Paclitaxel coated balloon

Paclitaxel is the pharmacologically active substance for anti-neointima. The active drug coating is located on the surface of the balloon, which contains 1.5 μg Paclitaxel per 1 mm2.

Drug: Aspirin

Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI.

Drug: Ticagrelor

Ticagrelor is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI.

Drug: Clopidogrel

Clopidogrel is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI when Ticagrelor is unfeasible or contradicted.

Active Comparator: Drug-eluting stent

Resolute Integrity Zotarolimus eluting stents will be used

Device: Resolute Integrity Zotarolimus eluting stents

The device consists of a balloon-expandable intracoronary drug-eluting stent pre-mounted on the MicroTrac Rapid Exchange stent delivery system. Drug eluting stent is composed of metal stent, primer and drug coating. The Stent is manufactured from a cobalt alloy (MP35N). The strut thickness is 88.9 μm and the length elements is 0.9 mm. The drug coating consists of the zotarolimus and BioLinx polymer (C10/C19/PVP) system. A coating of polymers loaded with zotarolimus in a formulation applied to the entire surface of the stent at a dose of approximately 1.6 µg/mm2 which results in a maximum nominal drug content of 380 µg on the largest stent (4.0 x 38 mm).

Drug: Aspirin

Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI.

Drug: Ticagrelor

Ticagrelor is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI.

Drug: Clopidogrel

Clopidogrel is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI when Ticagrelor is unfeasible or contradicted.

Outcome Measures

Primary Outcome Measures

Coronary fraction flow reserve (FFR) value [12 months]

Secondary Outcome Measures

In segment Late lumen loss (LLL) [12 months]
Key Secondary Outcome

Other Outcome Measures

Procedural success rate [7 days]
Procedural success rate included device success, lesion success and procedural success
Percentage of lesion segments diameter stenosis (DS%) [12 months]
Binary restenosis (DS% ≥ 50%) [12 months]
Target lesion failure (TLF) [1, 6, 12 months]
Target lesion failure (TLF), defined as cardiac death, target vessel myocardial infarction (TV-MI) and clinically indicated-target lesion revascularization (CI-TLR)
Patient-oriented composite endpoint (PoCE) [1, 6, 12 months]
Patient-oriented composite endpoint (PoCE) defined as all-cause death, any stroke, any MI, and any clinically and indicated revascularisation)
Definite/Probable Stent thrombosis rates [1, 6, 12 months]
Stent thrombosis included acute, subacute, late and very late thrombosis

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18y ≤ age ≤ 80y;
De-novo coronary artery lesions with indication for PCI;
Target lesion diameter stenosis ≥ 70% (visual) or ≥ 50% (visual) with evidence of ischemia;
Target lesion reference vessel diameter (2.5mm-4.0 mm), Length of a single target lesion ≤ 35mm; Total treated lesion length ≤ 60 mm;
Vessels treated ≤ 2; only one DCB/DES is allowed for each target vessel;
≤ 2 non-target lesions (non-TL) are allowed, and can not be in the same vessel as the target lesion (randomization should be implemented only after the successful treatment of all non-TL);
Patients who are able to complete the follow-up and compliant to the prescribed medication.

Exclusion Criteria:

Myocardial infarction (< 7 days);
Heavy thrombotic burden in target vessel;
eGFR < 30ml/min or hemodialysis patients;
Other cardiovascular and cerebrovascular percedures planned within 12 months after index PCI;
Patients with contraindications to antiplatelet agents and anticoagulants; or bleeding tendency, history of active peptic ulcer, and stroke within 6 months;
Life expectancy of less than 1 years;
Patient is a woman who is pregnant or nursing;
Known allergic to medications such as Aspirin, Heparin, antiplatelet drugs, paclitaxel, or contrast; patients with systemic lupus erythematosus or other systemic immune diseases;
Chronic total occlusion lesion;
Unprotected left main disease;
Bifurcation lesion requiring 2 stents;
Ostial lesions, distance from left main ≤ 2mm;
Severe calcification or distortion;
Arterial, venous or prosthetic grafts;
In-stent stenosis requiring revascularization (defined as stenosis≥50% by visual or positive functional assessments in any vessel);
Myocardial bridging located at target lesions;
Currently participating in another trial and not yet at its primary endpoint;
Participants deemed unsutable to be enrolled by investigators for unable to comply to protocol or other reasons.