CMOSS: The Carotid and Middle Cerebral Artery Occlusion Surgery Study

Sponsor

Xuanwu Hospital, Beijing (Other)

Overall Status

Completed

CT.gov ID

NCT01758614

Collaborator

(none)

330

Enrollment

Location

Arms

80.8

Actual Duration (Months)

4.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The recently published Carotid Occlusion Surgery Study (COSS) failed to show a benefit of extracranial-intracranial (EC-IC) bypass surgery over medical therapy in patients with symptomatic hemodynamically significant carotid occlusion. Since then on, different controversies have been raised on several aspects including the study population, qualifications of surgeons and hemodynamic evaluation.

In COSS protocol, the primary inclusion population is the patient demonstrating occlusion of unilateral ICA while the contralateral ICA less than 50% stenosis. Because of the enrollment problems, in the final result report, 18% patients suffered from contralateral ICA stenosis more than 50%. As we known, COSS utilized oxygen extraction fraction (OEF) ratio by PET as the criterion of hemodynamic evaluation. Bilateral ICAs lesion will disturbed the ratio even the identifying the subgroup of patients with hemodynamic insufficiency.

As an interventional trial, the COSS should ensure the certification for the experienced surgeons. While for expanding the number of centers and enhancing recruitment, COSS made some concessions on the surgeons training and certification. The 15% postoperative event rate is not the best that can be achieved according to recent surgical technical development.

The cerebral hemodynamic insufficiency has been considered as the primary pathophysiological factor for patients with ICA or MCA occlusion. For these patients, antiplatelet therapy is not likely to prevent hemodynamic stroke.EC-IC bypass surgery probably will be the possible effective therapy.

These underlying assumptions deserved further exploration and more strict research.So the CMOSS study in China is designed to compare the efficacy and safety of EC-IC bypass surgery with medical therapy in patients with symptomatic hemodynamically significant carotid occlusion.

Condition or Disease	Intervention/Treatment	Phase
Carotid Artery Occlusion Middle Cerebral Artery Occlusion Stroke	Procedure: bypass surgery Drug: Aspirin Drug: Clopidogrel	Phase 3

Detailed Description

Patients with symptoms of cerebral or retinal ischemia associated with ipsilateral internal carotid artery (ICA) occlusion have an annual risk of 5-8% of recurrent ischemic stroke. While in China, the incidence of middle cerebral artery (MCA) occlusion is higher than in western countries. The annual risk of recurrent ischemic stroke in patients with symptomatic ICA or MCA occlusion has not improved over the years. The proportion of recurrence that was minor disabling was rather high.

Study Design

Study Type:

Interventional

Actual Enrollment :

330 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Carotid and Middle Cerebral Artery Occlusion Surgery Study

Actual Study Start Date :

Jun 6, 2013

Actual Primary Completion Date :

Mar 2, 2018

Actual Study Completion Date :

Mar 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: bypass group all the participants in this group will be performed EC-IC bypass surgery	Procedure: bypass surgery all participants in this group will be performed EC-IC bypass surgery Other Names: EC-IC bypass surgery
Active Comparator: medical group all the participants in this group will be given medical therapy including aspirin 100mg per day or clopidogrel 75mg per day	Drug: Aspirin all participants in this group will be given medical therapy including Aspirin 100mg per day or clopidogrel 75mg per day Other Names: Aspirin 100mg per day or clopidogrel 75mg per day Drug: Clopidogrel

Arm

Intervention/Treatment

Experimental: bypass group

all the participants in this group will be performed EC-IC bypass surgery

Procedure: bypass surgery

all participants in this group will be performed EC-IC bypass surgery

Other Names:

EC-IC bypass surgery

Active Comparator: medical group

all the participants in this group will be given medical therapy including aspirin 100mg per day or clopidogrel 75mg per day

Drug: Aspirin

all participants in this group will be given medical therapy including Aspirin 100mg per day or clopidogrel 75mg per day

Other Names:

Aspirin 100mg per day or clopidogrel 75mg per day

Drug: Clopidogrel

Outcome Measures

Primary Outcome Measures

the number of participants who suffer from stroke or death after EC-IC bypass surgery or medical therapy [up to 30 days]
The number of participants who suffer from all stroke or death within 30 days after EC-IC bypass surgery or medical therapy
the number of participants who suffer from ipsilateral ischemic stroke [up to 24 months]
the number of participants who suffer from ipsilateral ischemic stroke within 24 months of randomization

Secondary Outcome Measures

the number of participants who suffer from severe transit ischemic attack (TIA) [up to 24 months of randomization]
the number of participants who suffer from severe TIA within 24 months of randomization
the number of participants who suffer from all stroke or death during 30 days to 24 months [during 30 days to 24 months]
the number of participants who suffer from all stroke or death during 30 days to 24 months
the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index [at 7 days, 30 days, 6 months, 12 months and 24 months]
the changes from baseline in mRS, NIHSS and Barthel Index at 7 days, 30 days, 6 months, 12 months and 24 months
the changes from baseline of cerebral blood flow (CBF) ratio in CT perfusion [at 24 months]
the changes from baseline of CBF ratio in CT perfusion at 24 months
the number of participants who suffer from all kinds of adverse events related to surgery [up to 30 days]
the number of participants who suffer from all kinds of adverse events related to surgery within 30 days in the EC-IC bypass surgery group

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ranging between 18 and 65 years;
Digital subtraction angiography imaging studies demonstrating occlusion of unilateral ICA or MCA;
Digital subtraction angiography imaging studies demonstrating less than 50% stenosis of any other vessels especially contralateral ICA and MCA;
Modified Rankin Scales (mRS) 0-2;
Qualifying TIA or ischemic stroke in the territory of the occluded ICA or MCA must have occurred within the past 12 months;
The most recent stoke attacked more than 3 weeks ago;
The neurological deficit must be stable for more than 1 month;
No massive cerebral infarction (>50% of the MCA territory) in CT or MRI study;
CT Perfusion demonstrates "misery perfusion" ;
Competent to give informed consent;
Legally an adult;
Geographically accessible and reliable for follow-up;

Exclusion Criteria:

Other neurovascular disease (such as cerebral aneurysm or arteriovenous malformation) conditions likely to cause focal cerebral ischemia;
Known unstable angina or myocardial infarction within recent 6 months;
Pregnant or perinatal stage women;
Blood coagulation dysfunction;
Any diseases likely to death within 2 years;
Past history of EC-IC bypass surgery;
Any contraindications or allergy to aspirin or clopidogrel;
Any heart disease likely to cause cerebral ischemia including prosthetic valves, infective endocarditis, atrial fibrillation, sick sinus syndrome, myxoma and cardiomyopathy with ejection fraction less than 25%;
Allergy to iodine or radiographic contrast media;
Serum creatinine > 3mg/dl;
Uncontrolled diabetes mellitus (fasting blood glucose >16.7mmol/l);
Uncontrolled hypertension (systolic BP >180 mmHg, diastolic BP>110 mmHg);
Severe liver dysfunction [alanine transaminase (ALT) and/or aspartate aminotransferase (AST) > 3 times of normal level];
Concurrent participation in any other experimental treatment trial;
Any condition that in the surgeon's judgment suggests the patient an unsuitable surgical candidate;