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

Study Overview
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Brief Summary
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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).

Official Title
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Paclitaxel-coated Balloon for the Treatment of De-novo Non-complex Coronary Artery Lesions: an Open-label, Multicentre, Randomised, Non-inferiority Trial

Conditions
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De Novo Stenosis, Coronary Artery Disease

Intervention / Treatment
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* Device: Paclitaxel coated balloon
* Device: Sirolimus eluting stents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 1. 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug-coated balloon<br> | Device: Paclitaxel coated balloon<br>* 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.<br>|
| Active Comparator: Drug-eluting stent<br> | Device: Sirolimus eluting stents<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device-oriented Composite Endpoint (DoCE) | DoCE is a composite clinical endpoint of Cardiac cause death, Target vessel myocardial infarction (TV-MI), and Clinically indicated target lesion revascularization (CI-TLR). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device-oriented Composite Endpoint (DoCE) | Rates of the DoCE beside the time point of primary endpoint | 1, 12, 36, and 60 months | 
| Cardiac cause death | Rates of individual components of the DoCE | 1, 12, 24, 36, and 60 months | 
| Target vessel myocardial infarction (TV-MI) | Rates of individual components of the DoCE | 1, 12, 24, 36, and 60 months | 
| Clinically indicated target lesion revascularization (CI-TLR) | Rates of individual components of the DoCE | 1, 12, 24, 36, and 60 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, 12, 24, 36, and 60 months | 
| All-cause death | individual components of PoCE | 1, 12, 24, 36, and 60 months | 
| Any MI | individual components of PoCE | 1, 12, 24, 36, and 60 months | 
| Any stroke | individual components of PoCE | 1, 12, 24, 36, and 60 months | 
| Any revascularisation | individual components of PoCE | 1, 12, 24, 36, and 60 months | 
| Any clinically indicated revascularisation |  | 1, 12, 24, 36, and 60 months | 
| Target vessel failure (TVF) | Target vessel failure, defined as cardiovascular death, TV MI and clinically-indicated target vessel revascularisation | 1, 12, 24, 36, and 60 months | 
| Clinical indicated target vessel revascularization |  | 1, 12, 24, 36, and 60 months | 
| Net adverse clinical events (NACE) | Net adverse clinical events (NACE), define as POCE or BARC type 3 or 5 bleeding events | 1, 12, 24, 36, and 60 months | 
| BARC type 3 or 5 bleeding events |  | 1, 12, 24, 36, and 60 months | 
| BARC defined type 2, 3 or 5 bleeding events |  | 1, 12, 24, 36, and 60 months | 
| Definite/Probable Stent thrombosis rates | According to ARC-II classification | 1, 12, 24, 36, and 60 months | 
| Device success | Device success is defined by the following: DCB: 1.Successful delivery within 120 seconds (DCB in vessel) of the DCB device at the intended target lesion; 2.DCB is successfully dilated for at least 30 seconds and the device system is successfully withdrawn; 3.After DCB dilation, the target vessel has no flow limiting dissection (type D, E and F); and the final in-lesion residual stenosis is less than 30% by core laboratory QCA (preferred methodology) or visual assessment; 4.No bailout procedure by stent; DES: 1.1. Successful delivery, balloon expansion, and deployment of the first assigned device, at the intended target lesion; 2.Successful withdrawal of the device delivery system; 3. 3. Attainment of a final in-stent residual stenosis of <20% by core laboratory QCA (preferred methodology) or visual assessment; | 0 day (during index PCI) | 
| Procedure success during PCI | Device success + without the occurrence of DoCE + no stent thrombosis at discharge during the index procedure hospital stay (maximum of 7 days). | 7 days | 
| Any ischemic or bleeding events | Time from randomization to the occurrence of first any ischemic or bleeding endpoints, including all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization and BARC-defined type 2 bleeding events | 1, 12, 24, 36, and 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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drug-coated balloons, percutaneous coronary intervention, de novo stenosis, drug-eluting stent