The Safety and Efficacy of DIOR Balloon in Coronary Bifurcation Lesions (BEYOND-II)

Comparison of the Safety and Efficacy Between Paclitaxel-Eluting Coronary Balloon Dilation Catheter (DIOR) and Paclitaxel-Eluting Balloon (Bingo) in Coronary Bifurcation Lesions: A Prospective, Multicenter, Randomized, Controlled Trial (BEYOND II)

To evaluate the safety and effectiveness of paclitaxel-eluting coronary artery balloon dilation catheter (DIOR) in revascularization of coronary bifurcation lesions compared with paclitaxel-eluting balloon (Bingo), and to provide the clinical data for the formal application in China and for the approvement of China marketing.

Study Overview

• Status: Unknown
• Conditions: Percutaneous Coronary Intervention
• Intervention / Treatment: Device: Paclitaxel-Eluting Coronary Balloon Dilation Catheter (DIOR); Device: Paclitaxel-Eluting Balloon (Bingo)

Detailed Description

This is a prospective, multicenter, randomize, control and non-inferior study. 220 patients with bifurcation lesions will be randomized 1:1 to each group. after the main branch has been treated successfully, and if the side branch's stenosis is more than 70% and can be pre-dilated by POBA (plain old balloon angioplasty) successfully, then randomizing. the patients in the study group will be treated with paclitaxel-eluting coronary artery balloon dilatation catheter (DIOR), while those in the control group will be treated with paclitaxel-eluting balloon (Bingo). Clinical follow-up will be conducted at baseline, operation, hospital discharge, 1 month, 6 months, 9 months and 12 months after operation, and angiographic follow-up will be conducted at 9 months. The primary endpoint is late lumen loss (LLL) in the balloon dilatation coverage area of side branch of at 9 month after operation. The secondary endpoints include device success, clinical success, target lesion failure (TLF), target lesion revascularization (TLR), clinical composite endpoints and imaging endpoints. The information of adverse events, serious adverse events and device defects will be collected during the study.

• Study Type: Interventional
• Enrollment (Anticipated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Bing Wang, professor; Phone Number: 86-024-28851120; Email: wangbindl@hotmail.com
• Study Contact Backup: Name: Geng wang, professor; Phone Number: 86-024-28851120; Email: wanggeng69@163.com

Study Locations

• China
  • Beijing, China
    • Beijing Anzhen Hospital Capital Medical University
  • Shanghai, China
    • Shanghai East Hospital,
    • Contact: Qi Zhang, professor; Phone Number: 86-021-38804518
  • Tianjin, China
    • Tianjin Chest Hospital
    • Contact: Hongliang Cong, professor; Phone Number: 86-022-88185003; Email: hongliangcong@163.com
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Daqing Oil General Hospital
      • Contact: Hui Li, professor; Phone Number: 86-0459-5805310
  • Hubei
    • Wuhan, Hubei, China
      • Wuhan Asian Heart Hospital
      • Contact: Xi Su, professor; Phone Number: 86-027-65796888; Email: yaxin_suxi@163.com
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing First Hospital
      • Contact: Saoliang Chen, professor; Phone Number: 86-025-52271351; Email: chmengx@126.com
  • Jilin
    • Changchun, Jilin, China
      • First Bethune Hospital of Jilin University
  • Liaonin
    • Dalian, Liaonin, China
      • The Second Hospital of Dalian University
    • Shengyang, Liaonin, China
      • General Hospital of Northern Theater Command
      • Contact: Geng wang, professor; Phone Number: 86-024-28851120; Email: wanggeng69@163.com
      • Contact: Han Yaling, professor; Phone Number: 86-024-28851120; Email: hanyaling@263.net
    • Shengyang, Liaonin, China
      • The First Hospital of China Medical University
      • Contact: Yingxian Sun; Phone Number: 86-024-83283166
  • Yunnan
    • Kunming, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
      • Contact: Guosheng Fu, professor; Phone Number: 86-0571-86090073; Email: fugs@medmail.com.cn
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital Zhejiang University School of Medicine
      • Contact: Wang jian'an, professor; Phone Number: 86-0571-87783777; Email: wangjianan@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects that participate in this study must fulfill all the following criteria:

General inclusion criteria:

1. Age from 18 to 80 years old, man or non-pregnant woman;
2. Subjects with stable or unstable angina, old myocardial infarction, or asymptomatic ischemic evidence with clinical diagnosis;
3. Subjects without contraindications of coronary artery bypass grafting (CABG);
4. Subjects must agree to the follow up of angiographic and clinical required in the study;
5. Subjects are able to understand the purpose of this study, provide an informed consent to show recognize to the study protocol.

Angiographic inclusion criteria:

1. One or two bifurcation lesions, locate in different epicardial vessels, the bifurcation lesion in each epicardial vessel can not over 1; or 1 de nove coronary artery bifurcation can be included after 1 lesion of non-target vessel has been successfully treated by PCI (Percutaneous Coronary Intervention);
2. Residual diameter stenosis in main branch (MB) ≥ 70% (visually), or ≥ 50% simultaneously with clinical symptom, and the diameter stenosis in side branch (SB) ≥ 50% (visually); and the main branch's residual stenosis ≤ 20% with TIMI 3 flow post the stent placement, while the side branch diameter stenosis ≥ 70% post the MB stenting;
3. Fulfill the definition of truly bifurcation lesions by Medina type (1.1.1、1.0.1、0.1.1);
4. Diameter in side branch between ≥ 2.5 mm to ≤ 4.00 mm (visually) and lesion length ≤ 26 mm (visually);
5. Each side branch of the bifurcation lesion can be treated by only 1 study drug coated balloon (DCB) or control DCB, and the lesion shall be fully covered by the DCB ( the distal end of the balloon shall exceed the lesion at least 1 mm).

Exclusion Criteria:

If subjects fulfill any of below criteria, this subject shall be exclude from this study.

General exclusion criteria:

1. Pregnant or lactating women
2. Any newly myocardial infarction onset within 1 week or, the myocardial enzyme of CK (Creatine Kinase) or CK-MB does not return to normal level after any myocardial infarction;
3. Cardiogenic shock;
4. Severe chronic heart failure, NYHA (New York Heart Association) ≥ grade III, or left ventricular ejection fraction < 35% (accessed by echocardiography or left ventricular angiography)
5. Patients with renal insufficiency (estimated glomerular filtration rate < 30ml/min/1.73m2 calculated by MRDR (Modification of Diet in Renal Disease) formula or subject is receiving renal dialysis)
6. Having a history of hemorrhagic diseases such as cerebral hemorrhage, gastrointestinal hemorrhage; stroke occurring or any situation occurring that may lead to prolongation of anticoagulation therapy within 6 months before operation;
7. History of coronary or peripheral vascular interventional therapy within 12 months before hospitalized.
8. Patients are allergic or contraindicate to contrast agent, paclitaxel, heparin, antiplatelet and anticoagulant drug;
9. The Subjects have other serious diseases and the expected survival is less than 12 months;
10. Investigators determine the subjects' compliance is poor, cannot complete the study as required;

Angiographic exclusion criteria

1. Main branch lesion or non-target lesion(s) located in left main;
2. Main branch lesion or non-target lesion(s) is triple vessel lesion, all need to be treated;
3. Side branch lesion is triple bifurcation or multiple bifurcation;
4. Main branch lesion located within 3 mm of the origin of the LAD (Left Anterior Descending), LCX (Left Circumflex Branch) or RCA (Right Coronary Arter);
5. Side branch target lesion is diffusion lesion and length > 26mm; or a ≥90% stenosis lesion is found near the SB lesion within 5 mm;
6. Side branch as the target vessel has received any interventional treatment;
7. Side branch as the target lesion or target vessel involve in aneurysm;
8. The lesion in side branch or main branch is total occlusive lesions, with TIMI blood flow of grade 0;
9. Side branch target lesion is moderate or heavy calcified or target vessel excessive tortuosity, which is unfavorable for interventional treatment anatomically;
10. Subject's blood pressure is too low to be injected with nitroglycerin ≥ 100 ug, this subject can not be included in the study;
11. Side branch target lesion can not reach the following outcomes, after the completely balloon pre-dilatation:

1) Residual stenosis (DS %) is ≤50% (visually); 2) TIMI Grade-3 flow ((visually); 3) No angiographic complications (e.g., no-reflow, distal embolization, side branch closure) 4) No dissections NHLBI grade C-F;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DIOR group; in this group, patients will be treated with Paclitaxel-Eluting Coronary Balloon Dilation Catheter (DIOR)	Device: Paclitaxel-Eluting Coronary Balloon Dilation Catheter (DIOR); patients in the study group will be treated by the Paclitaxel-Eluting Coronary Balloon Dilation Catheter (DIOR)
Active Comparator: Bingo group; in this group, patients will be treated with Paclitaxel-Eluting Balloon (Bingo)	Device: Paclitaxel-Eluting Balloon (Bingo); patients in the study group will be treated by the Paclitaxel-Eluting Balloon (Bingo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
late lumen loss	in balloon dilated coverage area of the side branch lesion measured by QCA (Quantitative Coronary Angiography)	9 months after operation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
device success	define as dilation success in the side branch lesion by study balloon or control ballon, that is the residual stenosis ≤50%，TIMI (Thrombolysis In Myocardial Infarction) 3 flow and without type C or above dissection	immediately post procedure
clinical success	define as absence of patients oriented composite endpoints (PoCE) during hospitalization, based on the device success.	1 month after operation
device oriented composite endpoints (DoCE)	that is TLF, define as the composite endpoint include cardiac death, target vessel myocardial infarction and ischemic driven target lesion revascularization (ID-TLR)	1, 6, 9, 12 month after operation
patients oriented composite endpoints (PoCE)	define as a composite endpoints of all cause death, any myocardial infarction and any revascularization	1, 6, 9, 12 month after operation
all cause death	include cardiac death, vascular death, noncardiovascular death	1, 6, 9, 12 month after operation
myocardial infarction (MI)	target vessel MI, non-target vessel MI	1, 6, 9, 12 month after operation
target lesion revasculation	ischemic driven, non-ischemic driven	1, 6, 9, 12 month after operation
target vessel revasculation	ischemic driven, non-ischemic driven	1, 6, 9, 12 month after operation
any coronary revasculation		1, 6, 9, 12 month after operation
thrombosis in the side branch lesion		1, 6, 9, 12 month after operation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
angiographic endpoints-late loss of side branch	assess in millimeter	9 months after operation
angiographic endpoints-minimal lumen diameter (MLD) of side branch	assess in millimeter	9 months after operation
angiographic endpoints-diameter stenosis (DS)	assess in percentage	9 months after operation
angiographic endpoints-angiographic binary restenosis (ABR)	assess in percentage	9 months after operation

Collaborators and Investigators

• Sponsor: CCRF Inc., Beijing, China
• Investigators: Principal Investigator: Yaling Han, professor, The General Hospital of Northern Theater Command

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2019
• Primary Completion (Anticipated): May 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 28, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: drug eluting balloon; bifurcation; coronary artery stenosis
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Albumin-Bound Paclitaxel
• Other Study ID Numbers: DIOR 2nd -1706

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No