Paclitaxel-coated Balloon for Treatment of De-novo Non-complex Coronary Artery Lesions
Study Details
Study Description
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).
Besides the ischemic events to be observed, there might be also a potential benefit of the DCB strategy by reducing the bleeding events. Although there is scarce evidence showing the optimal DAPT duration for DCB, in the current study, according to our empirical clinical experiences and previous expert consensus, the investigators chose aspirin + Ticagrelor/Clopidogrel for 3-month followed by Ticagrelor/Clopidogrel monotherapy for 3-month to be the antiplatelet regimen in DCB arm. In contrast to the antiplatelet regimen for the DES arm used in the current trial, which is aspirin + Ticagrelor/Clopidogrel for 3-month followed by Ticagrelor/Clopidogrel monotherapy for 9-month, the DCB and its antiplatelet strategy is estimated to reduce the bleeding events during follow-up.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Drug-coated balloon
|
Device: Swide Paclitaxel coated balloon
The Swide 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: Aspirin
Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI.
Drug: Ticagrelor or Clopidogrel for DCB
Ticagrelor or Clopidogrel is required for 6 months to be a part of the dual antiplatelet therapy (DAPT) after PCI.
|
| Active Comparator: Drug-eluting stent
|
Device: Firebird2 Sirolimus eluting stents
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: Aspirin
Aspirin is required for 3 months be a part of the dual antiplatelet therapy (DAPT) after PCI.
Drug: Ticagrelor or Clopidogrel for DES
Ticagrelor or Clopidogrel is required for 12 months to be a part of the dual antiplatelet therapy (DAPT) after PCI.
|
Outcome Measures
Primary Outcome Measures
- Device-oriented Composite Endpoint (DoCE) [24 months]
DoCE is a composite clinical endpoint of Cardiac cause death, Target vessel myocardial infarction (TV-MI), and Clinically indicated target lesion revascularization (CI-TLR).
Secondary Outcome Measures
- BARC defined type 2, 3 or 5 bleeding events [24 months]
Other Outcome Measures
- Device-oriented Composite Endpoint (DoCE) [12, 36 and 60 months]
Rates of the DoCE beside the time point of primary endpoint
- Cardiac cause death [12, 24, 36 and 60 months]
Rates of individual components of the DoCE
- Target vessel myocardial infarction (TV-MI) [12, 24, 36 and 60 months]
Rates of individual components of the DoCE
- Clinically indicated target lesion revascularization (CI-TLR) [12, 24, 36 and 60 months]
Rates of individual components of the DoCE
- Patient-oriented composite endpoint (PoCE) [12, 24, 36 and 60 months]
Patient-oriented composite endpoint (PoCE) defined as all-cause death, any stroke, any MI, and any clinically and indicated revascularisation)
- All-cause death [12, 24, 36 and 60 months]
individual components of PoCE
- Any MI [12, 24, 36 and 60 months]
individual components of PoCE
- Any stroke [12, 24, 36 and 60 months]
individual components of PoCE
- Any clinically indicated revascularisation [12, 24, 36 and 60 months]
individual components of PoCE
- Target vessel failure (TVF) [12, 24, 36 and 60 months]
Target vessel failure, defined as cardiovascular death, TV MI and clinically-indicated target vessel revascularisation
- Clinical indicated target vessel revascularization [12, 24, 36 and 60 months]
- Net adverse clinical events (NACE) [12, 24, 36 and 60 months]
Net adverse clinical events (NACE), define as POCE or BARC type 3 or 5 bleeding events
- BARC type 3 or 5 bleeding events [12, 24, 36 and 60 months]
- Definite/Probable Stent thrombosis rates [12, 24, 36 and 60 months]
According to ARC-II classification
- Device success [0 day (during index PCI)]
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;
- Procedure success during PCI [7 days]
Device success + without the occurrence of DoCE + no stent thrombosis at discharge during the index procedure hospital stay (maximum of 7 days).
- Win ratio comparison [24 months]
Results analysed by win ratio according to the hierarchical order of Death, BARC defined type 3 bleeding events, TV-MI, CI-TLR and BARC type 2 bleeding events
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with an indication for PCI due to acute or chronic coronary syndrome
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Patients with de-novo, non-complex lesion* and underwent successful pre-dilation**
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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
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Thrombolysis In Myocardial Infarction [TIMI] flow =3
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Without dissections type D, E, and F
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Residual stenoses <30% after balloon pre-dilation (visual).
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Without serious complication requiring the termination of PCI
Exclusion Criteria:
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Under the age of 18
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Unable to give informed consent
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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)
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Known contraindication to medications such as Heparin, antiplatelet drugs, or contrast.
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Currently participating in another trial and not yet at its primary endpoint
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The concurrent medical condition with a life expectancy of less than 2 years
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Previous intracranial hemorrhage
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In-stent stenosis requiring revascularization (defined as stenosis≥50% by visual or positive functional assessments in any vessel)
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Atrial fibrillation
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Prior CABG
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Cardiogenic shock
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ling Tao | Xi'an | Shannxi | China | 710032 |
Sponsors and Collaborators
- Xijing Hospital
Investigators
- Study Chair: 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 Documents (Full-Text)
None provided.More Information
Publications
None provided.- CAGE-FREE 1