MELAtonin for Prevention of Postoperative Agitation and Emergence Delirium in Children

Study Overview
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Brief Summary
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Postoperative agitation and emergence delirium describe a spectrum of symptoms of early postoperative negative behavior, in which the child experiences a variety of behavioral disturbances including crying, thrashing, and disorientation during early awakening from anaesthesia. The symptoms are common with a reported incidence of approximately 25%. Some clinical trials have studied the effect of prophylactic oral melatonin for reducing the risk of emergence agitation in children, some finding a considerable dose-response effect. Melatonin has a low bio-availability of approximately 15 %. The safety of exogenous melatonin for pediatric patients has been studied with no apparent serious adverse effects, even at repeated short-term use of high doses of intravenous melatonin. The aim of this clinical trial is to investigate the prophylactic effects and safety of intravenous melatonin administered intraoperatively for prevention of postopreative agitation and emergence delirium in children after an elective surgical procedure. The study is designed as a randomised, double-blind, placebo-controlled clinical trial.

Official Title
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MELAtonin for Prevention of Postoperative Agitation and Emergence Delirium in Children. The MELA-PAED Trial: a Randomized, Double-blind, Placebo-controlled Trial.

Conditions
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Emergence Delirium

Intervention / Treatment
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* Drug: Melatonin
* Drug: Isotonic sodium chloride solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 1-6 years Elective surgical procedure of en axpected duration of at least 30 minutes in general anesthesia maintained with sevoflurane Exclusion Criteria: Any known allergy or contraindication to study treatment or excipåients Current daily medication with melatonin

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melatonin<br>Participants receive melatonin solution for injection 1 mg/mL in a dosage of 0.15 mg/kg body weight as a single intravenous injection approximately 30 minutes before end of surgical procedure. | Drug: Melatonin<br>* Melatonin for injection 1 mg/mL<br>|
| Placebo Comparator: Placebo<br>Participants receive isotonic sodium chloride (9mg/mL) intravenously once approximately 30 minutes before end of surgical procedure in a volume equivalent to the melatonin group for the same weight. | Drug: Isotonic sodium chloride solution<br>* Sodium chloride 0.9 % for injection<br>* Other names: Normal saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of emergence agitation | Participants will be assessed on Watcha scale repeatedly ever 15 min during their stay at the Post-Anesthetic Care Unit. The variable is dichotomous: any score >2= Yes and no score <=2 = No | Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid consumption | The total amount of opioids administered for postoperative pain in the PACU will be evaluated as units of morphine equivalents per kg. No more than 35 % of the popu-lation is expected to receive postoperative opioids in a range of approximately 10-100 µg/kg. | Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU). | 
| Non-serious Adverse Events (AE) | Any untoward medical occurrence not considered serious. | From enrolment to the trial until 24-hour follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Melatonin, Sevoflurane, Postoperative Pain, Child, PONV