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

Official title

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)

Overview

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

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.

Interventions

• Device drug coated balloon
  Balloon/vessel diameter ratio 0.8-1.0, 8-12 ATM (atmosphere), lasting for \>30 seconds.
• Device drug eluted stent
  with regular techniques

Primary outcome measures

• The incidence rate of late lumen loss after percutaneous coronary intervention in patients with ISR [Time frame: Follow-up coronary angiography at 12 months after the procedure]

Secondary outcome measures (1)

• The incidence rate of patient-related ischemic events [Time frame: Clinical follow up at 30 days, 6, 9 and 12 months after the operation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Nanjing First Hospital — Nanjing

Publications

• Kolh P, Windecker S, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A; European Society of Cardiology Committee for Practice Guidelines; Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, B PMID 25173601
• Wong YTA, Kang DY, Lee JB, Rha SW, Hong YJ, Shin ES, Her SH, Nam CW, Chung WY, Kim MH, Lee CH, Lee PH, Ahn JM, Kang SJ, Lee SW, Kim YH, Lee CW, Park SW, Park DW, Park SJ. Comparison of drug-eluting stents and drug-coated balloon for the treatment of drug-eluting coronary stent restenosis: A randomized RESTORE trial. Am Heart J. 2018 Mar;197:35-42. doi: 10.1016/j.ahj.2017.11.008. Epub 2017 Nov 22. PMID 29447782
• Xu B, Tu S, Qiao S, Qu X, Chen Y, Yang J, Guo L, Sun Z, Li Z, Tian F, Fang W, Chen J, Li W, Guan C, Holm NR, Wijns W, Hu S. Diagnostic Accuracy of Angiography-Based Quantitative Flow Ratio Measurements for Online Assessment of Coronary Stenosis. J Am Coll Cardiol. 2017 Dec 26;70(25):3077-3087. doi: 10.1016/j.jacc.2017.10.035. Epub 2017 Oct 31. PMID 29101020

Identifiers

NCT: NCT04119986 · KY201910

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗