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.
Study Goal
The researchers aimed to determine whether melatonin is noninferior to midazolam in reducing preoperative anxiety in children undergoing elective surgery.
Results Summary
Melatonin was found to be inferior to midazolam in reducing preoperative anxiety, with clinically relevant differences observed. The trial was stopped early due to recruitment futility, increasing the likelihood of bias. No serious adverse events were reported in either group.
Population
Anxious children (median age 7 years, 52% female) awaiting day case elective surgery under general anesthesia.
Effective Dosage
0.5 mg/kg
Duration
Single dose administered preoperatively.
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
midazolam premedication | decrease | preoperative anxiety | anxious children awaiting day case elective surgery under general anaesthesia | - | was more effective than melatonin | #1 |
melatonin premedication | decrease | preoperative anxiety | anxious children awaiting day case elective surgery under general anaesthesia | - | was less effective than midazolam | #2 |
melatonin premedication | decrease | preoperative anxiety | anxious children awaiting day case elective surgery under general anaesthesia | - | was inferior to midazolam | #3 |
midazolam premedication | decrease | modified Yale Preoperative Anxiety Scale-Short Form score | anxious children awaiting day case elective surgery under general anaesthesia | 13.1 (3.7-22.4) | showed adjusted mean difference in favour of midazolam | #4 |
midazolam premedication | decrease | modified Yale Preoperative Anxiety Scale-Short Form score | anxious children awaiting day case elective surgery under general anaesthesia | 12.9 (3.1-22.6) | showed adjusted mean difference in favour of midazolam | #5 |
midazolam premedication | no change | serious adverse events | anxious children awaiting day case elective surgery under general anaesthesia | - | no serious adverse events were seen | #6 |
melatonin premedication | no change | serious adverse events | anxious children awaiting day case elective surgery under general anaesthesia | - | no serious adverse events were seen | #7 |
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 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.