Intravenous Magnesium Sulfate in Aneurysmal Subarachnoid Haemorrhage (IMASH)

Subarachnoid Hemorrhage Clinical Trial

Official title:

Phase 3 Study (Multi-center, Randomized Controlled Clinical Trial) of Intravenous Magnesium Sulfate to Improve Outcome After Aneurysmal Subarachnoid Haemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00124150
• Other study ID #: IMASH trial
• Status: Completed
• Phase: Phase 3
• First received: July 26, 2005
• Last updated: December 21, 2009
• Start date: June 2002
• Est. completion date: June 2009

Study information

• Verified date: July 2009
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Joint CUHK-NTEC Clinical Research Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The IMASH trial is a simple, randomized, double-blinded, placebo-controlled, multi-center trial to answer the question: "Does intravenous magnesium sulfate improve clinical outcome after aneurysmal subarachnoid hemorrhage?"

Description:

Vasospasm worsen outcome in patients with aneurysmal subarachnoid hemorrhage (ASAH).

Magnesium is known to dilate cerebral arteries and to block N-methyl-D-aspartate receptors in the injured neurons.

Intravenous magnesium may prevent vasospasm after subarachnoid hemorrhage and may protect neurons against damage during established vasospasm.

The IMASH trial is a randomized, placebo-controlled, double-blinded, multi-center trial to evaluate the effect that intravenous magnesium sulfate infusion on the clinical outcome of patients with aneurysmal subarachnoid haemorrhage.

Methods:

After obtaining randomisation code:

• Start MgSO4 20 mmol over 30 minutes, followed by infusion of 80 mmol/day or equivalent volume of saline within 48 h after onset of symptom,

• Study drug to be infused for 14 days from the day of hemorrhage (regarded as day 0).

• Measure plasma magnesium concentration daily and perform transcranial Doppler to monitor blood flow velocities of both middle cerebral arteries and extracranial segment of the internal carotid arteries.

• Plasma magnesium concentration in the IV MgSO4 group should be raised to 2.0-2.5 mmol/L or twice the serum baseline level. Patients that are randomized to saline infusion will only have their magnesium levels normalized if there is a clinical indication to do so.

Outcome assessment Primary outcome: Extended Glasgow Outcome Scale at six months Secondary outcome: Incidence of clinical vasospasm, Barthel Index; modified Rankin score, modified National Institute of Health Stroke Score, MCA velocities, other major complications

Study duration:

6 years with a refined sample size of 340 after analysis of pilot study data; with planned interim analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 327
• Est. completion date: June 2009
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• ASAH (as indicated by CT scan or lumbar puncture and an intracranial aneurysm confirmed by computer tomographic or conventional angiography)

• Within 48 hrs of ictus (hemorrhage event)

Exclusion Criteria:

• Pregnancy

• Major renal, hepatic or pulmonary disease

• Major cardiac disease or recent myocardial infarct (< 6 months)

• Age less than 18 years

• Moribund condition on admission (defined as a patient that is in such a poor clinical condition that further active neurosurgical management would not be anticipated)

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

Drug:
• Intravenous magnesium sulfate infusion
80mg per day

Locations

Country	Name	City	State
China	Department of Surgery, The Chinese University of Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (7)

Boet R, Chan MT, Poon WS, Wong GK, Wong HT, Gin T. Intravenous magnesium sulfate to improve outcome after aneurysmal subarachnoid hemorrhage: interim report from a pilot study. Acta Neurochir Suppl. 2005;95:263-4. — View Citation

Boet R, Mee E. Magnesium sulfate in the management of patients with Fisher Grade 3 subarachnoid hemorrhage: a pilot study. Neurosurgery. 2000 Sep;47(3):602-6; discussion 606-7. — View Citation

Boet R, Poon WS, Chan MT. Re: Magnesium: a useful adjunct in the prevention of cerebral vasospasm following aneurysmal subarachnoid haemorrhage. J Clin Neurosci. 2003 May;10(3):394. — View Citation

Wong GK, Chan MT, Boet R, Poon WS, Gin T. Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study. J Neurosurg Anesthesiol. 2006 Apr;18(2):142-8. — View Citation

Wong GK, Chan MT, Boet R, Poon WS. Correspondence to 'dose evaluation for long-term magnesium treatment in aneurysmal subarachnoid haemorrhage'. J Clin Pharm Ther. 2006 Aug;31(4):407. — View Citation

Wong GK, Chan MT, Poon WS, Boet R, Gin T. Magnesium therapy within 48 hours of an aneurysmal subarachnoid hemorrhage: neuro-panacea. Neurol Res. 2006 Jun;28(4):431-5. Review. — View Citation

Wong GK, Poon WS, Chan MT, Boet R, Gin T, Lam CW. The effect of intravenous magnesium sulfate infusion on serum levels of sodium and potassium in patients with aneurysmal subarachnoid hemorrhage. Magnes Res. 2007 Mar;20(1):37-42. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extended Glasgow Outcome Scale		At six months	No
Secondary	Incidence of clinical vasospasm		Within first 14 days	No
Secondary	Barthel Index		At six months	No
Secondary	Modified Rankin Score		At six months	No
Secondary	Modified National Institute of Health Stroke Score		At six months	No
Secondary	Other major complications requiring intensive care unit admission		During first 14 days	Yes

External Links

•   IMASH trial homepage