The Carotid and Middle Cerebral Artery Occlusion Surgery Study (CMOSS)
Primary Purpose
Carotid Artery Occlusion, Middle Cerebral Artery Occlusion, Stroke
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
bypass surgery
Aspirin
Clopidogrel
Sponsored by
About this trial
This is an interventional treatment trial for Carotid Artery Occlusion focused on measuring carotid artery occlusion, middle cerebral artery occlusion, EC-IC bypass surgery, stroke
Eligibility Criteria
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;
Sites / Locations
- Department of neurosurgery, Xuanwu hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
bypass group
medical group
Arm Description
all the participants in this group will be performed EC-IC bypass surgery
all the participants in this group will be given medical therapy including aspirin 100mg per day or clopidogrel 75mg per day
Outcomes
Primary Outcome Measures
the number of participants who suffer from stroke or death after EC-IC bypass surgery or medical therapy
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
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)
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
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
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
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
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
Full Information
NCT ID
NCT01758614
First Posted
December 24, 2012
Last Updated
November 11, 2021
Sponsor
Xuanwu Hospital, Beijing
1. Study Identification
Unique Protocol Identification Number
NCT01758614
Brief Title
The Carotid and Middle Cerebral Artery Occlusion Surgery Study
Acronym
CMOSS
Official Title
The Carotid and Middle Cerebral Artery Occlusion Surgery Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
June 6, 2013 (Actual)
Primary Completion Date
March 2, 2018 (Actual)
Study Completion Date
March 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xuanwu Hospital, Beijing
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carotid Artery Occlusion, Middle Cerebral Artery Occlusion, Stroke
Keywords
carotid artery occlusion, middle cerebral artery occlusion, EC-IC bypass surgery, stroke
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
330 (Actual)
8. Arms, Groups, and Interventions
Arm Title
bypass group
Arm Type
Experimental
Arm Description
all the participants in this group will be performed EC-IC bypass surgery
Arm Title
medical group
Arm Type
Active Comparator
Arm Description
all the participants in this group will be given medical therapy including aspirin 100mg per day or clopidogrel 75mg per day
Intervention Type
Procedure
Intervention Name(s)
bypass surgery
Other Intervention Name(s)
EC-IC bypass surgery
Intervention Description
all participants in this group will be performed EC-IC bypass surgery
Intervention Type
Drug
Intervention Name(s)
Aspirin
Other Intervention Name(s)
Aspirin 100mg per day or clopidogrel 75mg per day
Intervention Description
all participants in this group will be given medical therapy including Aspirin 100mg per day or clopidogrel 75mg per day
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Primary Outcome Measure Information:
Title
the number of participants who suffer from stroke or death after EC-IC bypass surgery or medical therapy
Description
The number of participants who suffer from all stroke or death within 30 days after EC-IC bypass surgery or medical therapy
Time Frame
up to 30 days
Title
the number of participants who suffer from ipsilateral ischemic stroke
Description
the number of participants who suffer from ipsilateral ischemic stroke within 24 months of randomization
Time Frame
up to 24 months
Secondary Outcome Measure Information:
Title
the number of participants who suffer from severe transit ischemic attack (TIA)
Description
the number of participants who suffer from severe TIA within 24 months of randomization
Time Frame
up to 24 months of randomization
Title
the number of participants who suffer from all stroke or death during 30 days to 24 months
Description
the number of participants who suffer from all stroke or death during 30 days to 24 months
Time Frame
during 30 days to 24 months
Title
the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index
Description
the changes from baseline in mRS, NIHSS and Barthel Index at 7 days, 30 days, 6 months, 12 months and 24 months
Time Frame
at 7 days, 30 days, 6 months, 12 months and 24 months
Title
the changes from baseline of cerebral blood flow (CBF) ratio in CT perfusion
Description
the changes from baseline of CBF ratio in CT perfusion at 24 months
Time Frame
at 24 months
Title
the number of participants who suffer from all kinds of adverse events related to surgery
Description
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
Time Frame
up to 30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Feng Ling, MD
Organizational Affiliation
Xuanwu Hospital, Beijing
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of neurosurgery, Xuanwu hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100053
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
22068990
Citation
Powers WJ, Clarke WR, Grubb RL Jr, Videen TO, Adams HP Jr, Derdeyn CP; COSS Investigators. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA. 2011 Nov 9;306(18):1983-92. doi: 10.1001/jama.2011.1610. Erratum In: JAMA. 2011 Dec 28;306(24):2672. Obviagele, Bruce [corrected to Ovbiagele, Bruce].
Results Reference
result
PubMed Identifier
21960571
Citation
Carlson AP, Yonas H, Chang YF, Nemoto EM. Failure of cerebral hemodynamic selection in general or of specific positron emission tomography methodology?: Carotid Occlusion Surgery Study (COSS). Stroke. 2011 Dec;42(12):3637-9. doi: 10.1161/STROKEAHA.111.627745. Epub 2011 Sep 29.
Results Reference
result
PubMed Identifier
22668888
Citation
Amin-Hanjani S, Barker FG 2nd, Charbel FT, Connolly ES Jr, Morcos JJ, Thompson BG; Cerebrovascular Section of the American Association of Neurological Surgeons; Congress of Neurological Surgeons. Extracranial-intracranial bypass for stroke-is this the end of the line or a bump in the road? Neurosurgery. 2012 Sep;71(3):557-61. doi: 10.1227/NEU.0b013e3182621488.
Results Reference
result
PubMed Identifier
9757852
Citation
Grubb RL Jr, Derdeyn CP, Fritsch SM, Carpenter DA, Yundt KD, Videen TO, Spitznagel EL, Powers WJ. Importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA. 1998 Sep 23-30;280(12):1055-60. doi: 10.1001/jama.280.12.1055.
Results Reference
result
PubMed Identifier
17494672
Citation
Waaijer A, van der Schaaf IC, Velthuis BK, Quist M, van Osch MJ, Vonken EP, van Leeuwen MS, Prokop M. Reproducibility of quantitative CT brain perfusion measurements in patients with symptomatic unilateral carotid artery stenosis. AJNR Am J Neuroradiol. 2007 May;28(5):927-32.
Results Reference
result
PubMed Identifier
27852286
Citation
Ma Y, Gu Y, Tong X, Wang J, Kuai D, Wang D, Ren J, Duan L, Maimaiti A, Cai Y, Huang Y, Wang X, Cao Y, You C, Yu J, Jiao L, Ling F. The Carotid and Middle cerebral artery Occlusion Surgery Study (CMOSS): a study protocol for a randomised controlled trial. Trials. 2016 Nov 16;17(1):544. doi: 10.1186/s13063-016-1600-1.
Results Reference
derived
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The Carotid and Middle Cerebral Artery Occlusion Surgery Study
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