Clinical trial NCT00124150: Intravenous Magnesium Sulfate in Aneurysmal Subarachnoid Haemorrhage (IMASH)
Official title: Phase 3 Study (Multi-center, Randomized Controlled Clinical Trial) of Intravenous Magnesium Sulfate to Improve Outcome After Aneurysmal Subarachnoid Haemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Subarachnoid Hemorrhage
Keywords: subarachnoid hemorrhage
magnesium sulfate
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2005-07-27
Enrollment: 327
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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?"

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Extended Glasgow Outcome Scale
timeFrame: At six months
Secondary outcomes:
measure: Incidence of clinical vasospasm
timeFrame: Within first 14 days
measure: Barthel Index
timeFrame: At six months
measure: Modified Rankin Score
timeFrame: At six months
measure: Modified National Institute of Health Stroke Score
timeFrame: At six months
measure: Other major complications requiring intensive care unit admission
timeFrame: During first 14 days
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Department of Surgery, The Chinese University of Hong Kong
Study officials:
affiliation: Department of Surgery, The Chinese University of Hong Kong
name: Wai S Poon, MB ChB FRCS
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1097/00006123-200009000-00014.
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. doi: 10.1016/s0967-5868(03)00006-7. No abstract available.
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.
citation: 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. doi: 10.1007/3-211-32318-x_53.
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. doi: 10.1097/00008506-200604000-00009.
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. doi: 10.1179/016164106X115035.
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. doi: 10.1111/j.1365-2710.2006.00728.x. No abstract available.
citation: Wong GK, Poon WS. Clinical, transcranial Doppler ultrasound, radiological features and, prognostic significance of delayed cerebral ischemia. Acta Neurochir Suppl. 2013;115:9-11. doi: 10.1007/978-3-7091-1192-5_3.
citation: Wong GK, Poon WS, Boet R, Chan MT, Gin T, Ng SC, Zee BC. Health-related quality of life after aneurysmal subarachnoid hemorrhage: profile and clinical factors. Neurosurgery. 2011 Jun;68(6):1556-61; discussion 1561. doi: 10.1227/NEU.0b013e31820cd40d.
citation: Wong GK, Poon WS, Chan MT, Boet R, Gin T, Ng SC, Zee BC; IMASH Investigators. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial. Stroke. 2010 May;41(5):921-6. doi: 10.1161/STROKEAHA.109.571125. Epub 2010 Apr 8.