Paclitaxel-coated Balloon for Treatment of De-novo Non-complex Coronary Artery Lesions

NCT04561739 | Active Not Recruiting DMC

• 1 other identifier: CAGE-FREE 1
• Study Type: interventional
• Target: 2,272
• Locations: 1 country
• Sites: 1

Brief Summary

The introduction of Bare-metal stents (BMS) since 1986 has alleviated the limitations of plain old balloon angioplasty (POBA) related elastic recoil and flow-limiting dissections. Later on, higher restenosis rates due to exaggerated neointimal growth in BMS has led to the development of drug-eluting stents (DES), which elutes an antiproliferative drug to the vessel wall and reduce the restenosis rate. However, 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). The advantages of DCB are that leaving no metal in the blood vessel and respect the vessel anatomy. Recently, studies with the strategy of DCB angioplasty with bailout stenting have demonstrated safety and efficacy for the small-vessel disease. In the BASKET-SMALL 2 trial, which compared SeQuent Please DCB with EES or Taxus DES in the vessels that have reference diameter\<3mm, showed that at 12-month follow-up, DCB was non-inferior to DES (MACE \[cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation\] rates: 8% vs. 9%). Although some small-scale RCT using surrogate endpoints have reported that no significant difference in MLD or late lumen loss between the two groups in large vessels, up to now, there is no large-scale RCT comparing the clinical outcomes of DCB versus DES in large vessels with de novo lesions. Therefore, the investigators hypothesized that in patients undergoing non-complex percutaneous coronary intervention (PCI) for de-novo stenoses, drug-coated balloon (DCB) is non-inferior to drug-eluting stents (DES).

Conditions

De Novo Stenosis; Coronary Artery Disease

Keywords

drug-coated balloons; percutaneous coronary intervention; de novo stenosis; drug-eluting stent

Outcome Measures

Primary Outcomes (1)

• Device-oriented Composite Endpoint (DoCE)

  DoCE is a composite clinical endpoint of Cardiac cause death, Target vessel myocardial infarction (TV-MI), and Clinically and physiologically indicated target lesion revascularization (CI-TLR).

  24 months

Secondary Outcomes (19)

• Device-oriented Composite Endpoint (DoCE)

  1, 12, 36, and 60 months

• Cardiac cause death

  1, 12, 24, 36, and 60 months

• Target vessel myocardial infarction (TV-MI)

  1, 12, 24, 36, and 60 months

• Clinically and physiologically indicated target lesion revascularization (CI-TLR)

  1, 12, 24, 36, and 60 months

• Patient-oriented composite endpoint (PoCE)

  1, 12, 24, 36, and 60 months

Study Arms (2)

Drug-coated balloon

EXPERIMENTAL

Device: Paclitaxel coated balloon

Drug-eluting stent

ACTIVE COMPARATOR

Device: Sirolimus eluting stents

Interventions

Paclitaxel coated balloon DEVICE

The Paclitaxel coated balloon is a paclitaxel-eluting rapid exchange balloon catheter for PTCA. Paclitaxel is the pharmacologically active substance for anti-neointima, whereas iopromide, a well-tolerated nonionic x-ray contrast agent, acts as a release-supporting additive. The active drug coating is located on the surface of the balloon, which contains 3 μg Paclitaxel per 1 mm2. The spray coating of the mixture of paclitaxel and iopromide of the Swide is via ultrasound, with the crystal size\<2um.

Drug-coated balloon

Sirolimus eluting stents DEVICE

The device has a backbone of L605 cobalt chromium. The stent has a open cell, in-phase, peak-to-valley design. The strut thickness is 86 μm and has a stent profile less than 1.12mm. The polymer coating of the stent is a styrene-butadiene block copolymer. The antiproliferative drug concentration is at 9 ug/mm, which 80% of the drug is released by 30 days.

Drug-eluting stent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with an indication for PCI due to acute or chronic coronary syndrome
• Patients with de-novo, non-complex lesion\* and underwent successful pre-dilation\*\*
• Patients who are able to complete the follow-up and compliant to the prescribed medication
• Non-complex PCI is defined as
• \. Vessels treated\<3; stents implanted\<3; lesions treated\<3 or Total stent length\<60 mm 2. Bifurcation does not require 2 stents 3. Non left main lesion 4. Non venous or arterial graft lesion 5. Non chronic total occlusion lesion 6. Do not require the use of atherectomy device
• \*\*Successful pre-dilation is defined as fulfilling all the following criteria
• Thrombolysis In Myocardial Infarction \[TIMI\] flow =3
• Without dissections type D, E, and F
• Residual stenoses \<30% after balloon pre-dilation (visual).
• Without serious complication requiring the termination of PCI

You may not qualify if:

• Under the age of 18
• Unable to give informed consent
• The patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
• Known contraindication to medications such as Heparin, antiplatelet drugs, or contrast.
• Currently participating in another trial and not yet at its primary endpoint
• The concurrent medical condition with a life expectancy of less than 2 years
• Previous intracranial hemorrhage
• In-stent stenosis requiring revascularization (defined as stenosis≥50% by visual or positive functional assessments in any vessel)
• Atrial fibrillation
• Prior CABG
• Cardiogenic shock

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Ling Tao

Xi'an, Shannxi, 710032, China

Location

Related Publications (5)

• Wang P, Zhou J, Gao H, Hu T, Sun D, Wang Q, Jiang H, Yin Z, Wen S, Jin Y, Chen H, Yuan M, Zhong L, Hu S, Lian Z, Jiang Z, Xia J, Liu J, Fu G, He X, Zhu B, Garg S, Onuma Y, Wang D, Serruys PW, Gao C, Tao L. Impact of sex on outcomes in patients treated with drug-coated balloons versus drug-eluting stents for de novo coronary artery lesions: Insights from the REC-CAGEFREE I trial. BMC Med. 2026 Jan 22. doi: 10.1186/s12916-026-04649-7. Online ahead of print.

  PMID: 41572254 DERIVED

• Bai X, Gao H, Lv Y, Sun D, Wang Q, Yin Z, Wen S, Jin Y, Chen H, Yuan M, Zhong L, Hu S, Lian Z, Zeng H, Pan H, Liu J, Fu G, Zhang R, He X, Capodanno D, Garg S, Onuma Y, Wang D, Serruys PW, Gao C, Tao L. Impact of Chronic Kidney Disease on Outcomes With Drug-Coated Balloons Versus Drug-Eluting Stents: Insights From the REC-CAGEFREE I Trial. Catheter Cardiovasc Interv. 2026 Jan;107(1):304-314. doi: 10.1002/ccd.70348. Epub 2025 Nov 20.

  PMID: 41264778 DERIVED

• Tao L, He X, Shen G, Wu M, He Y, Ma L, Yang F, Ji Z, Wang H, Wu Y, Fang Z, Jiang H, Wen S, Jin Y, Chen H, Zhong L, Hu S, Liu Y, Li F, Zhou J, Ouyang F, Zhang Z, Zhu B, Zhang R, Fu G, Liu J, Jiang Z, Wang D, Capodanno D, Garg S, Onuma Y, Serruys PW, Gao C; REC-CAGEFREE I Investigators. Drug-Coated Balloon Angioplasty vs Up-Front Stenting for De Novo CAD: 3-Year Follow-Up of REC-CAGEFREE I Trial. J Am Coll Cardiol. 2025 Oct 27:S0735-1097(25)09986-3. doi: 10.1016/j.jacc.2025.10.027. Online ahead of print.

  PMID: 41194754 DERIVED

• Gao C, He X, Ouyang F, Zhang Z, Shen G, Wu M, Yang P, Ma L, Yang F, Ji Z, Wang H, Wu Y, Fang Z, Jiang H, Wen S, Liu Y, Li F, Zhou J, Zhu B, Liu Y, Zhang R, Zhang T, Wang P, Liu J, Jiang Z, Xia J, van Geuns RJ, Capodanno D, Garg S, Onuma Y, Wang D, Serruys PW, Tao L; REC-CAGEFREE I Investigators. Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial. Lancet. 2024 Sep 14;404(10457):1040-1050. doi: 10.1016/S0140-6736(24)01594-0. Epub 2024 Sep 2.

  PMID: 39236727 DERIVED

• Gao C, He X, Liu Y, Liu J, Jiang Z, Zhu B, Qin X, Xia Y, Zhang T, Wang P, Zhang R, Onuma Y, Xia J, Wang D, Serruys P, Tao L. Drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design. BMC Cardiovasc Disord. 2024 Jun 24;24(1):319. doi: 10.1186/s12872-024-03974-0.

  PMID: 38914951 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Ling Tao, M.D., Ph.D.

  Xijing Hospital

  STUDY CHAIR

• Patrick Serruys, M.D., Ph.D.

  National University of Ireland, Galway

  STUDY CHAIR

• Yoshinobu Onuma, M.D., Ph.D.

  National University of Ireland, Galway

  STUDY CHAIR

• Chao Gao, M.D., Ph.D.

  Xijing Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Cardiology, Director of the department of Cardiology

Study Record Dates

• First Submitted: September 3, 2020
• First Posted: September 24, 2020
• Study Start: February 1, 2021
• Primary Completion: May 5, 2024
• Study Completion (Estimated): May 5, 2027
• Last Updated: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)