Paclitaxel-Coated Balloon Versus Zotarolimus-Eluting Stent for Treatment of De Novo Coronary Artery Lesions (CAGE-FREEIII)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Coronary Artery Disease; Percutaneous Coronary Intervention; De Novo Stenosis
• Intervention / Treatment: Drug: Aspirin; Device: Lepu Paclitaxel coated balloon; Drug: Ticagrelor; Drug: Clopidogrel; Device: Resolute Integrity Zotarolimus eluting stents

• Study Type: Interventional
• Enrollment (Actual): 370
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710032
      • Ling Tao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18y ≤ age ≤ 80y;
2. De-novo coronary artery lesions with an indication for PCI;
3. Target lesion diameter stenosis ≥ 70% (visual) or ≥ 50% (visual) with evidence of ischemia;
4. Target lesion reference vessel diameter (2.5mm-4.0 mm), Length of a single target lesion ≤ 35mm; Total treated lesion length ≤ 60 mm;
5. Vessels treated ≤ 2; only one DCB/DES is allowed for each target vessel;
6. ≤ 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);
7. Patients who are able to complete the follow-up and compliant to the prescribed medication.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug-coated balloon; Lepu Paclitaxel coated balloon will be used	Drug: Aspirin; Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI.; 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: 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	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.; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Coronary fraction flow reserve (FFR) value	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In segment Late lumen loss (LLL)	Key Secondary Outcome	12 months

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: Ling Tao, M.D, Ph.D, Xijing Hospital; Study Chair: Chao Gao, M.D, Ph.D, Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Estimated): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Fractional flow reserve; Percutaneous coronary intervention; Drug-eluting stent; Drug-coated balloons; De novo lesions
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Aspirin; Ticagrelor; Paclitaxel; Clopidogrel
• Other Study ID Numbers: CAGE-FREE III

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No