Safety and Efficacy of DCB Therapy for ISR Under the Guidance of QFR (UNIQUE-DCB-II Study )

Study Overview
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Brief Summary
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In 1970, the first percutaneous balloon coronary angioplasty opened a new chapter of interventional therapy. However, the incidence of intracoronary restenosis was about 30%. Subsequently, bare metal stents and drug-eluting stents (DES) reduced the incidence of in-stent restenosis (ISR) to 5%-10% and it was still a bottleneck treated by percutaneous coronary intervention (PCI). Currently, ISR is mainly treated by balloon angioplasty, stent implantation and coronary artery bypass grafting. In 2014, the guidelines of the European Society of Cardiology recommended that drug balloon therapy (DCB) and new generation DES should be the preferred strategies for ISR treatment. Compared with DES, DCB treatment can avoid the inflammation of intima caused by multi-layer stent strut, and reduce the risk of intimal hyperplasia and thrombosis in stent. However, DCB lacks sustained radial support. Even if the residual stenosis is less than 30% after sufficient pre-dilation, the elastic retraction of the intima still exists. In addition, the antiproliferative effect of paclitaxel is significantly worse than that of sirolimus and its derivatives, and there is a lack of long-term sustained release of anti-proliferative drugs. Compared with DCB, DES can obtain long-term stable radial support and long-term anti-proliferation effect, but stent struts exposed in the vascular lumen are at risk of stent thrombosis. The new generation of DES improves the design of stent platform, improves the polymer coating, and applies new anti-proliferative drugs. It effectively reduces the inflammation of vascular wall, speeds up the process of vascular re-endothelialization, promotes early vascular repair, and significantly reduces the incidence of stent thrombosis. Recent BIOLUXRCT, RESTORE and DARE studies provide more powerful evidence for the treatment of ISR by new generation DES. Quantitative flow ratio (QFR) is the second generation FFR detectional method based on coronary contrast image. The latest FAVOR II results also confirm that QFR is more sensitive and specific than quantitative coronary analysis (QCA) in the diagnosis of myocardial ischemia caused by coronary artery stenosis. However, there is no report of ISR treated with DCB under the guidance of QFR. The aim of this study was to evaluate the safety and efficacy of DCB in the treatment of in-stent restenosis in patients with coronary heart disease (CHD) under the guidance of QFR compared with DES implantation.

Detailed Description
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The current study is designed as a multicenter, randomized and prospective study aiming to evaluate the safety and efficacy of drug balloon therapy for ISR in patients with CHD under the guidance of QFR compared with DES implantation. Based on previous study reported, the incidence rate of target lesion failure is about 3% in patients with ISR undergoing DES implantation. And the design of non-inferiority study was performed in our study. Moreover, the investigators estimated 10% loss follow-up of these patients in each arm. As a result, a total of 220 patients with ISR were required, and with 110 patients per group as a ratio of 1:1 randomization.

Official Title
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Safety and Efficacy of Drug Coated Balloon Therapy for Coronary In-stent Restenosis in Patients With Coronary Heart Disease Under the Guidance of QFR (UNIQUE-DCB-II Study)

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Device: drug coated balloon
* Device: drug eluted stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ● Meet the diagnostic criteria for patients with coronary in-stent restenosis and QFR<0.8 of target lesion in the coronary stent Exclusion Criteria: QFR less than 0.8, dissection above type B and thrombosis formation after pre-dilation of ISR Severe congestive heart failure [LVEF <30% or NYHA( New York Heart Association) III/IV)] Severe valvular heart disease Life expectancy no more than 1 year or factors causing difficulties in clinical follow up Intolerance to aspirin and/or clopidogrel Known intolerance or allergy to heparin, contrast agents, paclitaxel, iopromide, rapamycin, polylactic acid-glycolic acid copolymer, Co-Cr alloy or platinum-chromium alloy Leukopenia or thrombopenia A history of peptic ulcer or GI bleeding in the previously Stroke within 6 months prior to the operation A history of severe hepatic or renal failure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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>A total of 110 patients with ISR are assigned to drug coated balloon treated group after randomization schedule. | Device: drug coated balloon<br>* Balloon/vessel diameter ratio 0.8-1.0, 8-12 ATM (atmosphere), lasting for >30 seconds.<br>|
| Other: drug eluted stent implantation<br>A total of 110 patients with ISR are assigned to drug eluted stent treated group after randomization schedule. | Device: drug eluted stent<br>* with regular techniques<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of late lumen loss after percutaneous coronary intervention in patients with ISR | The incidence rate of late lumen loss between DCB treated group and DES treated group evaluated by quantitative coronary analysis in patients with ISR | Follow-up coronary angiography at 12 months after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence rate of patient-related ischemic events | The incidence rate of patient-related ischemic events including all myocardial infarction, any revascularization and all-cause death | Clinical follow up at 30 days, 6, 9 and 12 months after the operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Quantitative flow ratio, drug coated balloon, Drug eluted stent, In-stent restenosis