The Adult Hemorrhagic Moyamoya Surgery Study (AHMSS)

The aim of this study is to investigate whether extracranial-intracranial(EC-IC) bypass surgery could prevent rebleeding and improve neurological function in adult moyamoya with hemorrhagic onset.

Study Overview

• Status: Active, not recruiting
• Conditions: Stroke; Moyamoya
• Intervention / Treatment: Procedure: Extracranial-intracranial bypass surgery

Detailed Description

About one half of adult moyamoya patients present with hemorrhagic onset.As the bleeding events are potentially fatal, it often lead to particularly poor prognosis.However, the natural history is still poorly understood.Although the rebleeding rate is known to be extremely high,no effective therapeutic method has been established based on a worldwide consensus.

The recently published Japanese Adult Moyamoya(JAM) Trial, which is the first prospective,randomized,controlled trial focused on hemorrhagic moyamoya,showed that direct bypass surgery could reduce the rebleeding rate and improve the prognosis.However,the result was statistically marginal with a small sample size and most importantly,it failed to assess the neurological function.The effect of bypass surgery on functional outcome was uncertain.

Therefore,the AHMSS study in China is designed to compare the efficacy and safety of EC-IC bypass surgery with conservative treatment in adult moyamoya patients with hemorrhagic onset by comprehensive assessment of rebleeding rate, neurological function.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200040
    • Department of Neurosurgery,Huashan Hospital,Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Independent in activity of daily living(The modified Rankin Scale 0-2)
2. At least one month since the most recent hemorrhagic stroke
3. The neurological deficit must be stable for more than 6 weeks
4. Bleeding in ventricle,cortex,basal ganglia,thalamus and subarachnoid space confirmed by computed tomography plain scan
5. Digital substraction angiography demonstrating progressive stenosis or occlusion in the terminal portion of the internal carotid artery and/or the initial portion of the anterior or middle cerebral arteries
6. Digital substraction angiography demonstrating formation of abnormal collateral networks(moyamoya vessels) at the base of the brain,mainly in the region of thalamus and basal ganglia
7. Digital substraction angiography demonstrating the vasculopathy appeared unilaterally or bilaterally
8. Competent to give informed consent
9. Accessible and reliable for follow-up

Exclusion Criteria:

1. Other cerebrovascular diseases(such as intracranial aneurysm or brain arteriovenous malformation) probably causing intracranial hemorrhage
2. Not independent in activity of daily living(The modified Rankin Scale 3-5)
3. Moyamoya syndrome concomitant with other hereditary or autoimmune diseases(Grave's Disease,Type I Diabetes Mellitus,Type I Neurofibromatosis et al)
4. Moyamoya disease with ruptured aneurysms located in the main stem of Willis' Circle
5. Emergent evacuation of intracerebral hematoma damaging superficial temporal artery or cortical artery
6. Emergent decompressive craniotomy causing automatically developed indirect revascularization
7. Good collateral networks formed by spontaneous anastomosis between extracranial and intracranial vessels before surgery
8. Life expectancy<1 years
9. Pregnancy
10. Unstable angina or myocardial infarction with recent 6 months
11. Blood coagulation dysfunction
12. Allergic to iodine contrast agent
13. Abnormal liver function(alanine transaminase(ALT) and/or aspartate aminotransferase(AST)>3 times of normal range)
14. Serum creatinine >3mg/dl
15. Poorly controlled hypertension(systolic BP>160 mmHg,diastolic BP>100 mmHg)
16. Poor glucose control(fasting blood glucose>16.7mmol/l)
17. Concurrent participation in any other interventional clinical trial

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
Active Comparator: Surgical intervention; All participants in this group will be assigned to receive extracranial-intracranial arterial bypass surgery.	Procedure: Extracranial-intracranial bypass surgery; All participants in this group will undergo combined cerebral revascularization surgery,namely superficial temporal to middle cerebral artery bypass (STA-MCA) and encephalo-duro-myo-synangiosis(EDMS); Other Names: STA-MCA Bypass and EDMS
No Intervention: Conservative management(medical management); All participants in this group will be assigned to receive conservative management or medical management which involves drug therapy as considered appropriate for medical symptoms by the treating investigator.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All strokes & death within 30 days post-surgery and ipsilateral recurrent bleeding afterwards	The number of participants who suffer from all strokes & death within 30 days post-surgery and ipsilateral recurrent bleeding afterwards within 5 years of randomization	within 5 years of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	up to 30 days
Rebleeding on the contralateral side	The number of participants who suffer from rebleeding on the contralateral side within 5 years of randomization	up to 5 years
Transient ischemic attack on the surgically treated side	The number of participants who suffer from TIA on the surgically treated side within 5 years of randomization	up to 5 years
The changes from baseline in modified Rankin Scale (mRS)	The changes from baseline in modified Rankin Scale (mRS) at 7 days, 30 days, 6 months, 12 months, 24 months，36 months，60 months or end of trial	at 7 days, 30 days, 6 months, 12 months, 24 months, 36 months, 60 months or end of trial
The changes from baseline in National Institute of Health Stroke Scale (NIHSS)	The changes from baseline in National Institute of Health Stroke Scale (NIHSS) at 7 days, 30 days, 6 months, 12 months, 24 months，36 months，60 months or end of trial	at 7 days, 30 days, 6 months, 12 months, 24 months, 36 months, 60 months or end of trial
The changes from baseline in modified Barthel Index	The changes from baseline in modified Barthel Index at 7 days, 30 days, 6 months, 12 months, 24 months，36 months，60 months or end of trial	at 7 days, 30 days, 6 months, 12 months, 24 months, 36 months, 60 months or end of trial

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Investigators: Study Chair: Yuxiang Gu, MD,PhD, Department of Neurosurgery,Huashan Hospital,Fudan University

Publications and helpful links

General Publications

• Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009 Mar 19;360(12):1226-37. doi: 10.1056/NEJMra0804622. No abstract available.
• Miyamoto S, Yoshimoto T, Hashimoto N, Okada Y, Tsuji I, Tominaga T, Nakagawara J, Takahashi JC; JAM Trial Investigators. Effects of extracranial-intracranial bypass for patients with hemorrhagic moyamoya disease: results of the Japan Adult Moyamoya Trial. Stroke. 2014 May;45(5):1415-21. doi: 10.1161/STROKEAHA.113.004386. Epub 2014 Mar 25.
• Derdeyn CP. Direct bypass reduces the risk of recurrent hemorrhage in moyamoya syndrome, but effect on functional outcome is less certain. Stroke. 2014 May;45(5):1245-6. doi: 10.1161/STROKEAHA.114.004994. Epub 2014 Mar 25. No abstract available.
• Kobayashi E, Saeki N, Oishi H, Hirai S, Yamaura A. Long-term natural history of hemorrhagic moyamoya disease in 42 patients. J Neurosurg. 2000 Dec;93(6):976-80. doi: 10.3171/jns.2000.93.6.0976.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: November 28, 2014
• First Submitted That Met QC Criteria: December 18, 2014
• First Posted (Estimate): December 19, 2014

Study Record Updates

• Last Update Posted (Estimate): February 17, 2016
• Last Update Submitted That Met QC Criteria: February 13, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Carotid Artery Diseases; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Moyamoya Disease
• Other Study ID Numbers: CAHMD 2014