MELAtonin for Prevention of Postoperative Agitation and Emergence Delirium in Children

Emergence Delirium Clinical Trial

— MELA-PAED  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05541276
• Other study ID #: 20211125
• Secondary ID: 2021-006464-24
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 1, 2024
• Est. completion date: January 1, 2027

Study information

• Verified date: April 2024
• Source: Rigshospitalet, Denmark
• Contact: Anne Louise B Garioud, MD
• Phone: +4535456243
• Email: anne.louise.de.barros.garioud[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: January 1, 2027
• Est. primary completion date: December 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Delirium
• Emergence Delirium

Intervention

Drug:
• Melatonin
Melatonin for injection 1 mg/mL
• Isotonic sodium chloride solution
Sodium chloride 0.9 % for injection

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Copenhagen Trial Unit, Center for Clinical Intervention Research, Sygehus Lillebaelt, University of Copenhagen

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious Adverse Events (SAE)	We will use the International Conference on Harmonization of technical require-ments for registration of pharmaceuticals for human use-Good Clinical Practice (ICH-GCP) definition of a serious adverse event, which is any untoward medical occurrence that resulted in death, was life-threatening, re-quired hospitalization or prolonging of existing hospitalization and resulted in persistent or significant disability or jeopardized the participant.	SAEs will be assessed from enrolment until 30 days after intervention.
Other	Postoperative pain	The incidence of postoperative pain will be assessed in each group according to the FLACC scale, assessed every 15 minutes in PACU. Postoperative pain is defined as any FLACC score >3.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Postoperative nausea and vomiting (PONV)	The incidence of PONV will be assessed dichotomously every 15 minutes in PACU. Outcome assessors will observe for vomiting. Nausea can be considered present if the participant refuses to eat and other causes are ruled out. There is no adequate PONV assessment tool available. PONV will be considered present if any assess-ment during PACU stay is "Yes".	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Time to administration of opioid	Time from end of anesthesia to the time point at which the first dose of opioid is administered in PACU. Not all participants (expectedly up to approximately 35%) will receive opioids in PACU.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Need for rescue medication	Dichotomous assessment of any administration in PACU of rescue medication specifically targeting EA according to treatment algorithm i.e., clonidine or propofol.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Time to awakening in PACU	Time from end of anesthesia to the first time point at which the participant is awake. If the participant is not awake two hours after arrival in PACU, a wake-up at-tempt will be carried out.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Time to postoperative oral intake	Time from end of anesthesia to the first time point at which the participant eats/drinks. All participants are assumed to eat/drink during their PACU stay.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Time for discharge readiness	Time from end of anesthesia (defined as above) to the time point at which partici-pant fulfills local discharge criteria. Discharge criteria will be evaluated by the re-sponsible physician prior to final discharge from PACU either to the participant's ward or to their home.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Emergence delirium	The incidence of emergence delirium will be evaluated according to the PAED score assessed every 15 minutes during PACU stay. The end-point is defined dichotomously as any score =10. Due to feasibility concerns, this outcome will solely be evaluated in a sub-population of approximately 50% of the trial population (200 participants), specifically only thos enrolled at the Juliane Marie Center Site.	Up to approximately 4 hours corresponding to stay in Post-Anesthetic Care Unit (PACU).
Other	Readmissions within 30 days	Assessed dichotomously counting day 0 as the day of discharge from hospital after the procedure. For the small group (expectedly <5 %) who will have had any read-missions within 30 days, the number of readmissions will be described.	From day of discharge + 30 days.
Primary	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	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).
Secondary	Non-serious Adverse Events (AE)	Any untoward medical occurrence not considered serious.	From enrolment to the trial until 24-hour follow-up.