PMID- 24144222 OWN - NLM STAT- MEDLINE DCOM- 20140602 LR - 20220129 IS - 2046-4924 (Electronic) IS - 1366-5278 (Print) IS - 1366-5278 (Linking) VI - 17 IP - 45 DP - 2013 Oct TI - MAGNEsium Trial In Children (MAGNETIC): a randomised, placebo-controlled trial and economic evaluation of nebulised magnesium sulphate in acute severe asthma in children. PG - v-vi, 1-216 LID - 10.3310/hta17450 [doi] AB - BACKGROUND: There are few data on the role of nebulised magnesium sulphate (MgSO4) in the management of acute asthma in children. Those studies that have been published are underpowered, and use different methods, interventions and comparisons. Thus, no firm conclusions can be drawn. OBJECTIVES: Does the use of nebulised MgSO4, when given as an adjunct to standard therapy in acute severe asthma in children, result in a clinical improvement when compared with standard treatment alone? DESIGN: Patients were randomised to receive three doses of MgSO4 or placebo, each combined with salbutamol and ipratropium bromide, for 1 hour. The Yung Asthma Severity Score (ASS) was measured at baseline, randomisation, and at 20, 40, 60 (T60), 120, 180 and 240 minutes after randomisation. SETTING: Emergency departments and children's assessment units at 30 hospitals in the UK. PARTICIPANTS: Children aged 2-15 years with acute severe asthma. INTERVENTIONS: Patients were randomised to receive nebulised salbutamol 2.5 mg (ages 2-5 years) or 5 mg (ages >/= 6 years) and ipratropium bromide 0.25 mg mixed with either 2.5 ml of isotonic MgSO4 (250 mmol/l, tonicity 289 mOsm; 151 mg per dose) or 2.5 ml of isotonic saline on three occasions at approximately 20-minute intervals. MAIN OUTCOME MEASURES: The primary outcome measure was the ASS after 1 hour of treatment. Secondary measures included 'stepping down' of treatment at 1 hour, number and frequency of additional salbutamol administrations, length of stay in hospital, requirement for intravenous bronchodilator treatment, and intubation and/or admission to a paediatric intensive care unit. Data on paediatric quality of life, time off school/nursery, health-care resource usage and time off work were collected 1 month after randomisation. RESULTS: A total of 508 children were recruited into the study; 252 received MgSO4 and 256 received placebo along with the standard treatment. There were no differences in baseline characteristics. There was a small, but statistically significant difference in ASS at T60 in those children who received nebulised MgSO4 0.25 [95% confidence interval (CI) 0.02 to 0.48]; p = 0.034 and this difference was sustained for up to 240 minutes [0.20 (95% CI 0.01 to 0.40), p = 0.042]. The clinical significance of this gain is uncertain. Assessing treatment-covariate interactions, there is evidence of a larger effect in those children with more severe asthma exacerbations ( p = 0.034) and those with a shorter duration of symptoms ( p = 0.049). There were no significant differences in the secondary outcomes measured. Adverse events (AEs) were reported in 19% of children in the magnesium group and 20% in the placebo group. There were no clinically significant serious AEs in either group. The results of the base-case economic analyses are accompanied by considerable uncertainty, but suggest that, from an NHS and Personal Social Services perspective, the addition of magnesium to standard treatment may be cost-effective compared with standard treatment only. The results of economic evaluation show that the probability of magnesium being cost-effective is over 60% at cost-effectiveness thresholds of pound1000 per unit decrement in ASS and pound20,000 per quality-adjusted life-year (QALY) gained, respectively; it is noted that for some parameter variations this probability is much lower, reflecting the labile nature of the cost-effectiveness ratio in light of the small differences in benefits and costs shown in the trial and the relation between the main outcome measure (ASS) and preference based measures of quality of life used in cost-utility analysis (European Quality of Life-5 Dimensions; EQ-5D). CONCLUSIONS: This study supports the use of nebulised isotonic MgSO4 at the dose of 151 mg given three times in the first hour of treatment as an adjuvant to standard treatment when a child presents with an acute episode of severe asthma. No harm is done by adding magnesium to salbutamol and ipratropium bromide, and in some individuals it may be clinically helpful. The response is likely to be more marked in those children with more severe attacks and with a shorter duration of exacerbation. Although the study was not powered to demonstrate this fully, the data certainly support the hypotheses that nebulised magnesium has a greater clinical effect in children who have more severe exacerbation with shorter duration of symptoms. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81456894. FUNDING: The National Institute for Health Research Health Technology Assessment programme. FAU - Powell, C V E AU - Powell CV AD - School of Medicine, Cardiff University, Cardiff, UK. FAU - Kolamunnage-Dona, R AU - Kolamunnage-Dona R FAU - Lowe, J AU - Lowe J FAU - Boland, A AU - Boland A FAU - Petrou, S AU - Petrou S FAU - Doull, I AU - Doull I FAU - Hood, K AU - Hood K FAU - Williamson, P R AU - Williamson PR CN - MAGNETIC study group LA - eng SI - ISRCTN/ISRCTN81456894 GR - 05/503/10/DH_/Department of Health/United Kingdom PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Health Technol Assess JT - Health technology assessment (Winchester, England) JID - 9706284 RN - 0 (Bronchodilator Agents) RN - 7487-88-9 (Magnesium Sulfate) SB - IM CIN - Evid Based Med. 2014 Jun;19(3):95. PMID: 24441079 MH - Acute Disease MH - Asthma/*drug therapy MH - Bronchodilator Agents/administration & dosage/adverse effects/*therapeutic use MH - Child MH - Child, Preschool MH - Cost-Benefit Analysis MH - Double-Blind Method MH - Drug Therapy, Combination MH - Emergency Service, Hospital MH - Female MH - Humans MH - Magnesium Sulfate/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Nebulizers and Vaporizers MH - Quality of Life MH - Severity of Illness Index PMC - PMC4781380 FIR - Powell, Colin IR - Powell C FIR - Russell, Ann IR - Russell A FIR - Howells, Anwen IR - Howells A FIR - Levy, David IR - Levy D FIR - Keane, Sonia IR - Keane S FIR - Fish, Claire IR - Fish C FIR - Al-Zidgali, Faisal IR - Al-Zidgali F FIR - Langworth, Sue IR - Langworth S FIR - Cook, Anne IR - Cook A FIR - Thomas, Zoe IR - Thomas Z FIR - Goldberg, Kate IR - Goldberg K FIR - Woods, Jacqueline IR - Woods J FIR - Bradley, Jacqueline IR - Bradley J FIR - Shenoy, Anil IR - Shenoy A FIR - Prady, Helena IR - Prady H FIR - Howell, Jane IR - Howell J FIR - Dolan, Jamie IR - Dolan J FIR - Mahmood, Dhia IR - Mahmood D FIR - Woods, Jacqueline IR - Woods J FIR - Thomas, Huw IR - Thomas H FIR - Payne, Victoria IR - Payne V FIR - Bingham, Tracey IR - Bingham T FIR - Moulsdale, Phoebe IR - Moulsdale P FIR - Harris, Adrian IR - Harris A FIR - Wilkins, Su IR - Wilkins S FIR - Curtis, Michelle IR - Curtis M FIR - Price, Layla IR - Price L FIR - Ward, Sue IR - Ward S FIR - Jayaram, Ravi IR - Jayaram R FIR - Burchett, Caroline IR - Burchett C FIR - Ho, Ang IR - Ho A FIR - Shippey, Joanne IR - Shippey J FIR - Gardner, Sharryn IR - Gardner S FIR - Zbaeda, Matouk IR - Zbaeda M FIR - Haslam, Zena IR - Haslam Z FIR - Morrison, Moira IR - Morrison M FIR - Ukwade, Patrick IR - Ukwade P FIR - Smith, Mark IR - Smith M FIR - Birak, Indy IR - Birak I FIR - Berry, Kathleen IR - Berry K FIR - Smith, Mark IR - Smith M FIR - Smith, Mark IR - Smith M FIR - Birak, Indy IR - Birak I FIR - Newton, Tina IR - Newton T FIR - Shepley, Hilary IR - Shepley H FIR - Beamond, Katharine IR - Beamond K FIR - Ahmed, Mansoor IR - Ahmed M FIR - Maiden, Jane IR - Maiden J FIR - Rawlins, Stephanie IR - Rawlins S FIR - Brooker, Richard IR - Brooker R FIR - Cameron, Lindsay IR - Cameron L FIR - Paton, James IR - Paton J FIR - Choudury, Vincent IR - Choudury V FIR - Kerr, Christine IR - Kerr C FIR - Scobie, Emma IR - Scobie E FIR - Pandya, Hitesh IR - Pandya H FIR - McFeeters, Melanie IR - McFeeters M FIR - Hunt, Samantha IR - Hunt S FIR - Carroll, Will IR - Carroll W FIR - Smith, Coral IR - Smith C FIR - Unsworth, Vanessa IR - Unsworth V FIR - Jones, Samantha IR - Jones S FIR - Watson, Nicola IR - Watson N FIR - Fitzsimmons, Chris IR - Fitzsimmons C FIR - Everard, Mark IR - Everard M FIR - Treherne, Katy IR - Treherne K FIR - Barber, Alyson IR - Barber A FIR - Dieppe, Clare IR - Dieppe C FIR - Vyas, Harish IR - Vyas H FIR - Smith, Helen IR - Smith H FIR - Hooton, Yvonne IR - Hooton Y FIR - Criddle, John IR - Criddle J FIR - Hodsdon, Lorraine IR - Hodsdon L FIR - Timms, Victoria IR - Timms V FIR - Parikh, Ami IR - Parikh A FIR - Ling, Frances IR - Ling F FIR - Barry, Gemma IR - Barry G FIR - Waithe, Pauleen IR - Waithe P FIR - Bayreuther, Jane IR - Bayreuther J FIR - Nsirim, Eniola IR - Nsirim E FIR - Smith, Michael IR - Smith M FIR - Gilpin, Sara IR - Gilpin S FIR - Armstrong, Damien IR - Armstrong D FIR - Brown, Julie IR - Brown J FIR - Potier, Katherine IR - Potier K FIR - Cook, Anne IR - Cook A FIR - Prady, Helena IR - Prady H FIR - Evans, Hazel IR - Evans H FIR - Long, Cilla IR - Long C FIR - Casey, Michelle IR - Casey M FIR - Tuladhar, Anil IR - Tuladhar A FIR - Paturi, Venkata IR - Paturi V FIR - Nozedar, Catherine Tarn IR - Nozedar CT EDAT- 2013/10/23 06:00 MHDA- 2014/06/03 06:00 PMCR- 2016/03/07 CRDT- 2013/10/23 06:00 PHST- 2013/10/23 06:00 [entrez] PHST- 2013/10/23 06:00 [pubmed] PHST- 2014/06/03 06:00 [medline] PHST- 2016/03/07 00:00 [pmc-release] AID - 10.3310/hta17450 [doi] PST - ppublish SO - Health Technol Assess. 2013 Oct;17(45):v-vi, 1-216. doi: 10.3310/hta17450.