Intravenous Magnesium Sulfate in Aneurysmal Subarachnoid Haemorrhage (IMASH)

Study Overview
=================
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.

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

Conditions
-----------------
Subarachnoid Hemorrhage

Intervention / Treatment
-----------------
* Drug: Intravenous magnesium sulfate infusion


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M<br>Intravenous magnesium sulfate infusion for 14 days. | Drug: Intravenous magnesium sulfate infusion<br>* 80mg per day<br>|
| No Intervention: S<br>Saline infusion without additional magnesium sulfate. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extended Glasgow Outcome Scale |  | At six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinical vasospasm |  | Within first 14 days | 
| Barthel Index |  | At six months | 
| Modified Rankin Score |  | At six months | 
| Modified National Institute of Health Stroke Score |  | At six months | 
| Other major complications requiring intensive care unit admission |  | During first 14 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
subarachnoid hemorrhage, magnesium sulfate