Judith Cohen and Mike Bradburn, along with the Chief Investigator Professor Steve Goodacre (Health Services Research) and other colleagues in ScHARR and elsewhere have recently been involved in the analysis and reporting of a randomised controlled trial (RCT) to evaluate the effectiveness of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma.
The 3Mg trial: a randomised controlled trial of intravenous or nebulised magnesium sulphate versus placebo in adults with acute severe asthma
Authors: Goodacre S, Cohen J, Bradburn M, Stevens J, Gray A, Benger J, Coats T
Journal: Health Technology Assessment Volume: 18 Issue: 22
Publication date: April 2014 DOI: 10.3310/hta18220
Magnesium sulphate, administered by the intravenous (i.v.) or inhaled (nebulised) route, has been proposed as a treatment for adults with acute severe asthma. Existing trials show mixed results and uncertain evidence of benefit. The 3Mg trial aimed to determine whether i.v. or nebulised magnesium sulphate improves symptoms of breathlessness and reduces the need for hospital admission in adults with acute severe asthma.
Adults (aged 16 or more) with acute severe asthma were recruited from the emergency departments of 34 acute hospitals in the UK, then randomly allocated to one of three groups:
1) i.v. magnesium sulphate (2 g over 20 minutes)
2) nebulised magnesium sulphate (3 × 500 mg over 1 hour)
3) or standard therapy alone.
The main outcome measures were the proportion of patients admitted to hospital (either after emergency department treatment or at any time over the subsequent 7 days) and breathlessness measured on a 100-mm visual analogue scale (VAS) over 2 hours after initiation of treatment.
One thousand one hundred and nine consenting participants were randomised to: i.v. magnesium sulphate (406 patients), nebulised magnesium sulphate (339 patients) and 364 to standard therapy. Hospital admission was recorded for 394, 332 and 358 patients, respectively, and VAS breathlessness for 357, 296 and 323 patients respectively. Intravenous magnesium sulphate was associated with an odds ratio (OR) of 0.73 [95% confidence interval (CI) 0.51 to 1.04; p = 0.083] for hospital admission, an improvement in VAS breathlessness that was 2.6 mm (95% CI -1.6 to 6.8 mm; p = 0.231) greater than that associated with standard therapy and an improvement in PEFR that was 2.4 l/minute (95% CI -8.8 to 13.6 l/minute; p = 0.680) greater than that associated with standard therapy. Nebulised magnesium sulphate was associated with an OR of 0.96 (95% CI 0.65 to 1.40; p = 0.819) for hospital admission, an improvement in VAS breathlessness that was 2.6 mm (95% CI -1.8 mm to 7.0 mm; p = 0.253) less than that associated with standard therapy and an improvement in PEFR that was 2.6 l/minute (95% CI -9.2 to 14.5 l/minute; p = 0.644) less than that associated with standard therapy. There were no significant differences between i.v. or nebulised magnesium sulphate and placebo for any other outcomes.
The research was unable to demonstrate a clinically worthwhile benefit from magnesium sulphate in acute severe asthma. There was some weak evidence of an effect of i.v. magnesium sulphate on hospital admission, but no evidence of an effect on VAS breathlessness or PEFR compared with standard therapy. The research team found no evidence that nebulised magnesium sulphate was more effective than standard therapy.
The RCT was funded by the NIHR Health Technology Assessment (HTA) Programme.