Extracranial-intracranial Bypass Surgery for Symptomatic Chronic Middle Cerebral Artery Occlusion: the CMOSS-2 Trial

Extracranial-intracranial Bypass Surgery Versus Medical Treatment Alone for Symptomatic Chronic Middle Cerebral Artery Occlusion: the CMOSS-2 Trial

The CMOSS-2 trial is a government-funded, prospective, multicenter, randomized controlled trial. It will recruit symptomatic chronic occlusion of the middle cerebral artery in patients with severe hemodynamic insufficiency. Only high-volume center with a proven track record will be included. Patients will be randomized (1:1) to best medical treatment alone or medical treatment plus bypass surgery. Primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization.

Study Overview

• Status: Recruiting
• Conditions: Infarction, Middle Cerebral Artery; Symptomatic Chronic Middle Cerebral Artery Occlusion
• Intervention / Treatment: Procedure: Extracranial-Intracranial Bypass Surgery; Other: Medical treatment alone

Detailed Description

Middle cerebral artery occlusion is an important cause of ischemic stroke, and there are currently two treatment methods: medical treatment alone and extracranial-intracranial bypass surgery (EC-IC bypass surgery). Previous studies have shown that the optimal medical treatment has an annual stroke recurrence rate of up to 10%, and patients with concomitant hemodynamic disorders can also increase by 7.3 times.

The CMOSS study was the first trial in China to evaluate the safety and efficacy of EC-IC bypass surgery on patients with ICA or MCA occlusion combined with hemodynamic insufficiency evaluated with CT perfusion. The results showed that there was no significant difference in the risk of stroke or death between the bypass group and the medical group, but there was a significant difference in ipsilateral ischemic stroke between 30 days and 2 years after randomization, with only 2.0% in the surgery group and 10.3% in the medical group; In addition, subgroup analysis found that for patients with MCA occlusion or severe hemodynamic insufficiency, bypass surgery has a potential beneficial trend over medical treatment alone.

The CMOSS-2 trial is a government-funded, prospective, multicenter, randomized controlled trial. It will recruit symptomatic chronic occlusion of the middle cerebral artery in patients with severe hemodynamic insufficiency. Only high-volume center with a proven track record will be included. Patients will be randomized (1:1) to best medical treatment alone or medical treatment plus bypass surgery. Primary outcome is ischemic stroke in the territory of the target artery within 24 months after randomization. The CMOSS-2 trial will be conducted in 13 sites in China.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tao Wang, MD; Phone Number: 18810302298; Email: wangtao_dr@sina.com
• Study Contact Backup: Name: Yan Ma, MD; Phone Number: 13810669502; Email: leavesyan@sina.com

Study Locations

• China
  • Beijing, China, 100053
    • Recruiting
    • Xuanwu Hospital, Capital Medical University.
    • Contact: Liqun Jiao, MD; Phone Number: 13911224991; Email: liqunjiao@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age of 18-65 years;
2. Confirmed as chronic occlusion of unilateral middle cerebral artery (MCA) by digital subtraction angiography (DSA) or computed tomography angiography (CTA). Other cerebral artery stenosis should be less than 50%.
3. CT perfusion demonstrates severe hemodynamic insufficiency in the territory of the qualifying MCA with MTT (symptomatic side) ≥ 6s or rCBF (symptomatic side/contralateral side) ≤ 0.8;
4. mRS score is 0-2 points;
5. A history of ischemic events (including<1/2 cerebral infarction in the middle cerebral artery supply area, or transient ischemic attack [TIA]) related to the qualifying artery within 12 months ;
6. The onset of acute stroke should be more than 1 month;
7. CT or MRI excludes large cerebral infarction (infarction>1/2 of the territory of the qualifying middle cerebral artery);
8. Patients or their guardians voluntarily participate of the study and sign the consent form.

Exclusion Criteria:

1. History of intracranial hemorrhage, subarachnoid hemorrhage, subdural hemorrhage, or extradural hemorrhage within 6 weeks;
2. Unstable angina pectoris or myocardial infarction, congestive heart failure within 6 months;
3. Women who are pregnant or lactating;
4. Coagulation dysfunction or hemorrhagic tendency (e.g. INR > 1.5 and/or platelet count < 100,000 mcL);
5. Other diseases with a life expectancy of less than 2 years
6. Previous treatment with EC-IC bypass surgery
7. Known allergy or contraindication to aspirin or clopidogrel or other antiplatelet drugs.
8. Known cardiac conditions that may lead to cardiogenic embolism: including prosthetic valves, infective endocarditis, left atrial or left ventricular thrombosis, atrial fibrillation, sick sinus node syndrome, atrial mucinous tumor or cardiomyopathy, ejection fraction <25%;
9. Allergy to iodine or x-ray contrast, blood creatinine > 3.0 mg/dl or other contraindications to arteriography
10. Uncontrolled diabetes mellitus with fasting blood sugar (FBS) >16.7 mmol/L
11. Uncontrolled hypertension with a sitting systolic blood pressure >180 mmHg or a sitting diastolic blood pressure >110 mmHg;
12. Persistent worsening of neurological symptoms within 72 hours;
13. Severe liver dysfunction, defined as serum alanine transaminase (ALT) and/or glutamic oxalacetic transaminase (AST) > 3 times the upper limit of normal range;
14. Active peptic ulcer disease;
15. Having received a clinical trial drug or device within 30 days prior to screening, or being enrolled in another clinical trial;
16. Other diseases or medical history that, in the judgment of the investigator, may affect the efficacy or safety evaluation of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Surgery; The patients in the surgical group will be treated with direct extracranial to intracranial bypass surgery plus best medical treatment.	Procedure: Extracranial-Intracranial Bypass Surgery; Extracranial-intracranial bypass surgery plus medical treatment
Active Comparator: Medical treatment; The patients will receive medical treatment alone according to the AHA/ASA Stroke and Transient Ischemic Attack (TIA) Stroke Prevention Guidelines (2021 edition).	Other: Medical treatment alone; Best medical treatment alone according to current clinical guidelines, including antiplatelet drugs (e.g. aspirin) and risk factor controls.; Other Names: Best medical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ischemic stroke in territory of qualifying artery	Number of participants with ischemic stroke in territory of qualifying artery within 2 years after randomization	2 years after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any stroke or death	Number of participants with any stroke or death within 30 days after randomization	30 days after randomization
A composite of any stroke or death within 30 days, or ischemic stroke in territory of qualifying artery beyond 30 days to 2 years after randomization	Number of participants with any stroke or death within 30 days, or ischemic stroke in territory of qualifying artery beyond 30 days to 2 years after randomization	within 2 years after randomization
Number of participants with any stroke	Number of participants with any stroke within 2 years after randomization	within 2 years after randomization
Number of participants with disabling stroke (mRS>3)	Number of participants with disabling stroke within 2 years after randomization	within 2 years after randomization
Number of participants with fatal stroke (death caused by a stroke)	Number of participants with fatal stroke within 2 years after randomization	within 2 years after randomization
Number of participants with death	Number of participants with death within 2 years after randomization	within 2 years after randomization
Number of participants with any stroke or death	Number of participants with any stroke or death within 2 years after randomization	within 2 years after randomization
Functional outcomes of participants	Functional outcomes of participants such as modified Rankin scale (mRS) or the National Institutes of Health Stroke Scale (NIHSS) at 2 years after randomization	2 years after randomization
Anastomosis patency of participants in surgical group	Anastomosis patency of participants in surgical group at 2 years after randomization	2 years after randomization

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Liqun Jiao, MD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 23, 2023
• First Submitted That Met QC Criteria: June 9, 2023
• First Posted (Actual): June 12, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: stroke; TIA; middle cerebral artery occlusion
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Necrosis; Ischemia; Intracranial Arterial Diseases; Stroke; Cerebral Arterial Diseases; Cerebral Infarction; Infarction; Arterial Occlusive Diseases; Infarction, Middle Cerebral Artery
• Other Study ID Numbers: CMOSS-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No