Clinical trial NCT01758614: The Carotid and Middle Cerebral Artery Occlusion Surgery Study
Official title: The Carotid and Middle Cerebral Artery Occlusion Surgery Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carotid Artery Occlusion
Middle Cerebral Artery Occlusion
Stroke
Keywords: carotid artery occlusion
middle cerebral artery occlusion
EC-IC bypass surgery
stroke
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2013-01-01
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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;

Primary outcomes:
measure: the number of participants who suffer from stroke or death after EC-IC bypass surgery or medical therapy
timeFrame: up to 30 days
measure: the number of participants who suffer from ipsilateral ischemic stroke
timeFrame: up to 24 months
Secondary outcomes:
measure: the number of participants who suffer from severe transit ischemic attack (TIA)
timeFrame: up to 24 months of randomization
measure: the number of participants who suffer from all stroke or death during 30 days to 24 months
timeFrame: during 30 days to 24 months
measure: the changes from baseline in mRS, national institutes of health stroke scale (NIHSS) and Barthel Index
timeFrame: at 7 days, 30 days, 6 months, 12 months and 24 months
measure: the changes from baseline of cerebral blood flow (CBF) ratio in CT perfusion
timeFrame: at 24 months
measure: the number of participants who suffer from all kinds of adverse events related to surgery
timeFrame: up to 30 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of neurosurgery, Xuanwu hospital
state: Beijing
Study officials:
affiliation: Xuanwu Hospital, Beijing
name: Feng Ling, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.