Intravenous Magnesium Sulfate in Aneurysmal Subarachnoid Haemorrhage (IMASH)

Completed

Phase 3 Results N/A

Trial Description

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.

Conditions

Interventions

  • Magnesium Drug
    Intervention Desc: Ion channel blocker (blocks voltage gated calcium channels and NMDA receptors)
  • Intravenous magnesium sulfate infusion Drug
    Intervention Desc: 80mg per day
    ARM 1: Kind: Experimental
    Label: M
    Description: Intravenous magnesium sulfate infusion for 14 days.

Trial Design

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

Patient Involvement

Patients will be randomized and then 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.

Outcomes

Type Measure Time Frame Safety Issue
Primary Extended Glasgow Outcome Scale at six months.
Secondary Incidence of clinical vasospasm; Barthel Index; Modified Rankin score; Modified National Institute of Health Stroke Score; middle cerebral artery (MCA) velocities; other major complications.
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

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