Simple Crossover Versus Side Branch Opening in Patients With Non-Left Main Bifurcation Lesion (CROSS-COBIS)

Randomized Controlled Trial of Simple CROSSsover Versus Side Branch Opening on Clinical Outcomes in Patients With Non-Left Main BIfurcation LeSion (CROSS-COBIS)

Hypothesis:

Simple crossover strategy would be non-inferior to SB opening strategy in the risk of target lesion failure (TLF) in patients with angiographically compromised SB (visually SB stenosis ≥50%) after provisional MV stenting for non-left main bifurcation lesion.

A total of 1000 patients (500 per each group) with the angiographically compromised SB (visually SB stenosis ≥50%) after provisional MV stenting for non-left main bifurcation lesion will be enrolled. Patients will be randomized to either the simple crossover strategy group or SB opening strategy group at the time of enrollment with 1:1 ratio. Stratified randomization according to participating center, clinical presentation (acute coronary syndrome or stable ischemic heart disease), and type of bifurcation lesions (true or non-true) will be performed.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Procedure: Simple Crossover; Procedure: Side branch opening

Detailed Description

Despite advances in stenting techniques and devices, percutaneous coronary intervention (PCI) for bifurcation lesions remains one of the most challenging and complex procedures. Current guidelines recommend 1-stenting with provisional side branch (SB) approach should be an initial treatment strategy for the bifurcation lesions, based on the previous results of several randomized trials. However, the standardization of the provisional strategy is limited. In particular, there is a recommendation on the treatment technique for SB when SB intervention is required, but It has not been decided in which cases SB treatment is necessary, in the latest European Bifurcation Club (EBC) consensus document.16 In previous studies, the criteria for performing SB opening after MV stent intervention in the 1-stenting with provisional SB approach were varied. In the DK-CUSH II (Double Kissing Crush versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions) or CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) trials, SB intervention was performed when the SB diameter stenosis more than 50%, grade B or higher dissection, or blood flow disturbance (TIMI flow 2 or less) after MV stent insertion. On the other hand, in the Nordic trial, the authors applied strict criteria for SB intervention after MV stent insertion (TIMI flow 2 or less only). Furthermore, there have been conflicting results regarding the clinical and angiographic outcomes of the jailed SB opening strategy after the main vessel (MV) stenting, compared with the simple crossover strategy for non-left main bifurcation lesion.

On this background, this trial aims to compare the clinical outcomes between simple crossover and side branch opening strategies in patients with the angiographically compromised SB (visually SB stenosis ≥50%) after provisional MV stenting for non-left main bifurcation lesion.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chang-Wook Nam, MD; Phone Number: 82-53-258-7019; Email: namcwcv@gmail.com
• Study Contact Backup: Name: Ki Hong Choi; Phone Number: 82-2-3410-6653; Email: cardiokh@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• (1) Subject must be at least 19 years of age
• (2) Patients with non-left main bifurcation lesion (SB diameter ≥2.3 mm)
• (3) Target lesions amenable for 1-stenting with provisional SB approach by operators' decision
• (4) Angiographically compromised SB (visual SB stenosis ≥50%) after provisional MV stenting

Exclusion Criteria:

• (1) Target lesions requiring elective 2-stenting technique by operators' decision (Observation Group 1)*

• (2) Patients who inevitably require SB intervention after MV stenting, as follows. (Observation Group 2)*

  1. Reduced SB TIMI flow (≤2) after MV stenting
  2. SB dissection after MV stenting (≥ Type C)
• (3) Patients without SB compromise after MV stenting (visually SB stenosis <50%) (Observation Group 3)*
• (4) Cardiogenic shock (Killip class IV) at presentation
• (5) Patients with significant valvular heart disease or severe left ventricular systolic dysfunction (ejection fraction <35%)
• (6) Pregnancy or breast feeding
• (7) Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment)
• (8) Unwillingness or inability to comply with the procedures described in this protocol

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: Simple crossover arm; This arm will receive the main vessel stenting only (with proximal optimization technique).	Procedure: Simple Crossover; Regardless of allocated arms, stent implantation in the MV (selected 1:1 according to the distal MV size) followed by systematic proximal optimization technique (POT, post-dilatation of the stent at the level of proximal MV with a balloon diameter sized 1:1 according to the proximal MV) or POT like procedure is strongly recommended.
Active Comparator: Side branch opening arm; This arm will receive a side branch opening procedure after the main vessel stenting.	Procedure: Side branch opening; According to the latest European Bifurcation Club (EBC) consensus document, distal SB rewiring followed by kissing balloon inflation (eventually conducted with short non-compliant balloons) and repeat POT procedures are highly recommended. An additional stent will be allowed if major dissection or decreased TIMI flow of SB occurs during SB treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Target-lesion failure	a composite of cardiac death, myocardial infarction, and target-lesion revascularization	up to 2 years of median follow-up (till 1 year after the last patient enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause death	Death from any causes	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Cardiac death	Death from cardiac causes	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Myocardial infarction	any myocardial infarction	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Target-vessel myocardial infarction	myocardial infarction in target-vessel	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Target-lesion revascularization	Clinically indicated target-lesion revascularization	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Target-vessel revascularization	Clinically indicated target-vessel revascularization	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Any revascularization	Repeat revascularization procedure	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Stent thrombosis	definite or probable stent thrombosis by Academic Research Consortium [ARC] definition	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Bleeding	Bleeding ARC type 2, 3 or 5 bleeding	up to 2 years of median follow-up (till 1 year after the last patient enrollment)
Total procedure time	procedure time	at 1 day
Total amount of contrast use	used contrast amount	at 1 day
Incidence of contrast induced nephropathy	defined as an increase in creatinine of ≥0.5mg/dL or ≥25% from baseline within 72 hours after contrast exposure	72 hours after the index procedure

Collaborators and Investigators

• Sponsor: Keimyung University Dongsan Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): March 31, 2028
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: January 26, 2023
• First Posted (Estimate): January 30, 2023

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 26, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Percutaneous coronary intervention; Bifurcation; Side branch; Treatment strategy
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease
• Other Study ID Numbers: CROSS-COBIS

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