Evaluation of the Efficacy and Safety of a Paclitaxel Eluting PTCA Balloon Catheter in Coronary In-stent Restenosis

Study Overview
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Brief Summary
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Over the past two decades, stents implantation has developed as a standard treatment for coronary stenosis lesions. However, int-stent restenosis (ISR) was one of the main factors affecting the long-term efficacy of coronary artery interventional therapy, with the incidence of ISR after percutaneous coronary intervention ranging from 5% to 35%. At present, there are three main means for ISR: (1) simple balloon dilation; 2) intravascular radiotherapy; and (3) drug elution stent. But the results are still not ideal. Drug coated balloon (DCB) is a new method that may be used to treat ISR in recent years. In the PEPCAD II study, when dealing with ISR, the paclitaxel eluting balloon (PEB) SeQuent® Please significantly reduced the major adverse cardiovascular events (MACEs) compared to the paclitaxel eluting stent (PES) TAXUS Liberte. In ISR-I and ISR-II trial, it was found that compared with uncoated PTCA balloons, PEB could significantly inhibit endothelial hyperplasia and significantly reduce MACEs treating ISR. The purpose of this study was to assess the efficacy and safety of a Chinese-developed PEB in treatment of coronary ISR compared to SeQuent® Please PEB.

Official Title
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Evaluation of the Efficacy and Safety of a Paclitaxel Eluting PTCA Balloon Catheter in Coronary In-stent Restenosis: a Randomized, Open-label, Positive Parallel Controlled, Multicenter Clinical Trial

Conditions
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Coronary In-stent Restenosis

Intervention / Treatment
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* Device: Paclitaxel eluting PTCA balloon
* Device: SeQuent® Please paclitaxel eluting balloon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients oriented Patients with age between 18 and 80 years old (including 18 and 80 years old); Patients with stable angina, or unstable angina pectoris, or old myocardial infarction (MI) or with evidence of local myocardial ischemia although without symptoms; Patients with restenosis after the first time stent implantation of de novo coronary lesions (i.e., no other surgical treatments for the target lesions except for the first stent implantation); Patients with the willing to receive their own coronary angioplasty; Patients with LVEF>30% measured within 30 days before recruitment; Patients agree to receive 9-month angiography follow-up, and agree to receive 30 days, 6 months, 12 months clinical follow-up; Patients at the age of childbirth must take effective contraception measures until the study is completed since they are chosen into screening period; Patients agree to take part in the trial and sign the informed consent. Lesions oriented (Visual estimation) Patients with Mehran type I, type II and type III in-stent restenosis (ISR); Reference vascular diameter between 2.0-4.0 mm (including 2.0 and 4.0 mm), length<30mm; The percent of lumen ISR ≥70%, or ≥50% with local ischemia evidence before interventional surgery; Patients with residual stenosis ≤30%, and ≤ type B dissection post pretreatment; Distance between other lesions that require treatment and target lesions >10 mm; Patients with coronary artery anatomy allowing delivery of research device to target lesions. Exclusion Criteria: Patients oriented Subjects with consistent clinical symptoms and/or ECG changes and/or cardiac enzymes changes with MI (including STEMI and Non-STEMI) within one week; Subjects with cardiac shock, hemodynamic instability or refractory ventricular arrhythmia that require positive inotropic drugs or mechanical circulation support; Subjects with one of following conditions (from screening period to the day of operation): (1) life expectancy is less than 1 year because of other severe diseases (like cancer), (2) drug abuse at present (like alcohol, cocaine, heroin and so on), (3) plan to accept surgery that may cause the programs not to be complied with or confusing with data understanding; Subjects with bleeding diathesis or active gastrointestinal ulcers, or stroke/transient ischemic attack within 3 months; Subjects with severe congestive heart failure or severe heart failure at the level of NYHA IV; Subjects are receiving dialysis or baseline serum creatinine levels>2.0 mg/dL(177μmol/L); Subjects with severe valvular heart disease; Subjects who have been or are scheduled for a heart transplantation during the trial; Subjects who have been pregnant or is planning to be pregnant or is breastfeeding during the trial; Subjects who are participating in any other clinical trial; Researchers don't think they're suitable for the trial because of other reasons; Lesions oriented (Visual estimation) Total occlusion with TIMI 0 (Mehran IV stenosis); With the evidence of widespread thrombi in the target vessels prior to intervention; Planning to treat >3 lesions (i.e., up to 3 target lesions); Planning to treat >2 major epicardial vessels (i.e., up to 2 target lesions); Planning to treat a single lesions with more than 1 balloon; Planning to treat a true bifurcation lesion with double stents technique; Left main lesions. Combined medication oriented Subjects known to intolerant to dual antiplatelet therapy for 3 months post interventional treatment (e.g., aspirin and/or ticagrelor and/or clopidogrel); Subjects with leukopenia (WBC<3x10^9/L for more than 3 days) or neutropenia (NEUT<1x10^9/L for more than 3 days) or a history of platelet reduction (PLT 30x10^9/L); Subjects known to be intolerant or allergic to paclitaxel.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Paclitaxel eluting PTCA balloon<br>Treatment of coronary in-stent restenosis with paclitaxel eluting PTCA balloon | Device: Paclitaxel eluting PTCA balloon<br>* Treatment of coronary in-stent re-stenosis with paclitaxel eluting PTCA balloon<br>|
| Active Comparator: SeQuent® Please paclitaxel eluting balloon<br>Treatment of coronary in-stent restenosis with SeQuent® Please paclitaxel eluting balloon | Device: SeQuent® Please paclitaxel eluting balloon<br>* Treatment of coronary in-stent re-stenosis with SeQuent® Please paclitaxel eluting balloon<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of target lesion late lumen loss |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of interventional therapy success | Including rate of device success, rate of disease success and rate of clinical success | 0-24 hours, 30 days, 6 months, 9 months, 12 months | 
| Rate of target lesion restenosis |  | 9 months | 
| Device-oriented composite clinical cardiovascular outcomes | Cardiac death, target vessel-related myocardial infarction, symptoms-driven target lesion revascularization | 30 days, 6 months, 9 months, 12 months | 
| Patient-oriented composite clinical cardiovascular outcomes | All-cause mortality, all myocardial infarction, all revascularization | 30 days, 6 months, 9 months, 12 months | 
| Rate of ARC defined thrombosis events | All definite, probable and possible thrombosis in acute, subacute and late stage | 0-24 hours, 30 days, 6 months, 9 months, 12 months |