The MAGIC trial : a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
BACKGROUND: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results.
METHODS: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg-1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals.
RESULTS: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm.
CONCLUSION: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias.
CLINICAL TRIAL REGISTRATION: ISRCTN registry: ISRCTN18296119.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:132 |
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| Enthalten in: |
British journal of anaesthesia - 132(2024), 1 vom: 26. Jan., Seite 76-85 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bolt, Robert [VerfasserIn] |
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| Links: |
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| Themen: |
General anaesthesia |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 21.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bja.2023.10.011 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Bolt, Robert |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The MAGIC trial |b a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia |
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| 500 | |a Date Revised 21.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a BACKGROUND: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results | ||
| 520 | |a METHODS: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg-1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals | ||
| 520 | |a RESULTS: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm | ||
| 520 | |a CONCLUSION: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias | ||
| 520 | |a CLINICAL TRIAL REGISTRATION: ISRCTN registry: ISRCTN18296119 | ||
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| 700 | 1 | |a Herbert, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Papaioannou, Diana E |e verfasserin |4 aut | |
| 700 | 1 | |a Totton, Nikki |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Matthew J |e verfasserin |4 aut | |
| 700 | 1 | |a Clarkson, Janet |e verfasserin |4 aut | |
| 700 | 1 | |a Evans, Christopher |e verfasserin |4 aut | |
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| 700 | 1 | |a Norrington, Amy C |e verfasserin |4 aut | |
| 700 | 1 | |a Paton, Robert H |e verfasserin |4 aut | |
| 700 | 1 | |a Vernazza, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Deery, Christopher |e verfasserin |4 aut | |
| 700 | 0 | |a MAGIC collaborative |e verfasserin |4 aut | |
| 700 | 1 | |a Albadri, Sondos |e investigator |4 oth | |
| 700 | 1 | |a Armstrong, Laura |e investigator |4 oth | |
| 700 | 1 | |a Atkins, Simon |e investigator |4 oth | |
| 700 | 1 | |a Babb, Margaret |e investigator |4 oth | |
| 700 | 1 | |a Biercamp, Claire |e investigator |4 oth | |
| 700 | 1 | |a Biggs, Katie |e investigator |4 oth | |
| 700 | 1 | |a Bradburn, Mike |e investigator |4 oth | |
| 700 | 1 | |a Buckley, Jaimie |e investigator |4 oth | |
| 700 | 1 | |a Child-Cavill, Julie |e investigator |4 oth | |
| 700 | 1 | |a Cope, Sean |e investigator |4 oth | |
| 700 | 1 | |a Crawley, Simon |e investigator |4 oth | |
| 700 | 1 | |a Dimairo, Munya |e investigator |4 oth | |
| 700 | 1 | |a Duro, Enass |e investigator |4 oth | |
| 700 | 1 | |a Eissa, Ayman |e investigator |4 oth | |
| 700 | 1 | |a Flight, Laura |e investigator |4 oth | |
| 700 | 1 | |a Gath, Jacqui |e investigator |4 oth | |
| 700 | 1 | |a Gavel, Gil |e investigator |4 oth | |
| 700 | 1 | |a Geary, Tim |e investigator |4 oth | |
| 700 | 1 | |a Gilchrist, Fiona |e investigator |4 oth | |
| 700 | 1 | |a Gopal, Padma |e investigator |4 oth | |
| 700 | 1 | |a Hall, Jamie |e investigator |4 oth | |
| 700 | 1 | |a Hutchence, Kate |e investigator |4 oth | |
| 700 | 1 | |a Khandelwal, Puran |e investigator |4 oth | |
| 700 | 1 | |a Kukreja, Pranav |e investigator |4 oth | |
| 700 | 1 | |a Leeuwenberg, Ian |e investigator |4 oth | |
| 700 | 1 | |a Limb, James |e investigator |4 oth | |
| 700 | 1 | |a Loban, Amanda |e investigator |4 oth | |
| 700 | 1 | |a Mellor, Katie |e investigator |4 oth | |
| 700 | 1 | |a Masip, Nuria |e investigator |4 oth | |
| 700 | 1 | |a Moores, Anthony |e investigator |4 oth | |
| 700 | 1 | |a Oshan, Vimmi |e investigator |4 oth | |
| 700 | 1 | |a Pickles, Edward |e investigator |4 oth | |
| 700 | 1 | |a Ray, Jaydip |e investigator |4 oth | |
| 700 | 1 | |a Rodd, Helen |e investigator |4 oth | |
| 700 | 1 | |a Rolfe, Sian |e investigator |4 oth | |
| 700 | 1 | |a Sheldon, Elena |e investigator |4 oth | |
| 700 | 1 | |a Simmonds, Richard |e investigator |4 oth | |
| 700 | 1 | |a Smith, Rachel |e investigator |4 oth | |
| 700 | 1 | |a Sundar, Ashok |e investigator |4 oth | |
| 700 | 1 | |a Thomason, Anna |e investigator |4 oth | |
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| 700 | 1 | |a Young, Tracey |e investigator |4 oth | |
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