Melatonin vs Midazolam in Children Undergoing Tonsillectomy

NCT07336095 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: FMASU MS 206/2025
• Study Type: interventional
• Target: 195
• Locations: 0 countries
• Sites: N/A

Brief Summary

Used as a premedication to decrease anxiety (Caumo et al., 2007). Midazolam, though has several drawbacks (McCann and Kain, 2001). Hence, an alternative premedication to midazolam will definitely have a widespread appeal. Melatonin is a hormone secreted by the pineal gland. Melatonin is different from benzodiazepines and their derivatives in that it exerts a promoting effect on sleep by amplifying day/night differences in alertness and sleep quality and displaying a modest sleep-inducing effect, quite mild as compared to that seen with benzodiazepines (Ahmad et al., 2007). Melatonin has also been reported to cause preoperative anxiolysis and an increase in levels of sedation without impairing orientation (Naguib and Samarkandi, 2000). Hence, the aim of this study is to compare the effect of oral melatonin and oral midazolam on preoperative anxiety. Emergence delirium (ED) was first described in the literature in the early 1960s. Although often used interchangeably with emergence agitation, it is defined as a temporary dissociated state of consciousness after discontinuation of anesthesia. The characteristics that make up ED include irritability, inconsolable crying, distress and inability to cooperate (Reduque and Verghese, 2013). Midazolam is the most prescribed oral premedication in the preoperative setting. Its benefits include preoperative anxiolysis, amnesia, relatively rapid onset and short duration of action. Although most children have anxiolysis with midazolam, up to 29% may display a paradoxical agitation response (Shin et al., 2013). Oral melatonin doses up to 0.4 mg/kg (maximum 20 mg) are effective in reducing ED in children (age 3-7 years) (Kain et al., 2009). AIM OF THE WORK The study aims to compare the effects of oral melatonin and oral midazolam on preoperative anxiety as a premedication in children undergoing tonsillectomy.

Conditions

Emergence Delirium, Anesthesia; Child; Anxiety; Midazolam Premedication; Melatonin Bioavailability; Tonsillectomy

Keywords

melatonin, midazolam, anxiety, children, tonsillectomy

Outcome Measures

Primary Outcomes (1)

• Incidence of preoperative anxiety with oral melatonin vs oral midazolam as a premedication in Children Undergoing Tonsillectomy.

  Assessment of sedation 30 min after the drug administration using Ramsay sedation scale.

  30 minutes after giving the drug

Secondary Outcomes (1)

• 1. Effect of both drugs in reducing incidence of post operative emergence delerium

  24 hours afer the procedure

Study Arms (3)

Melatonin group (Group M)

ACTIVE COMPARATOR

All patients will be subjected to a thorough medical history, physical examination, routine preoperative investigations will be done to all children including laboratory investigations as (complete blood picture, bleeding time, prothrombin time and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operation room. Parental presence will be allowed throughout sedation and post sedation period. Patients will be randomly assigned to three groups first group(M group) will receive 0.3 mg per kg oral melatonin in 10 ml Dextrose 10% 45 min before surgery )Maximum dose 10mg). Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

Drug: Melatonin group

Midazolam group (Group D)

SHAM COMPARATOR

All patients will be subjected to a thorough medical history, physical examination, routine preoperative investigations will be done to all children including laboratory investigations as (complete blood picture, bleeding time, prothrombin time and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operation room. Parental presence will be allowed throughout sedation and post sedation period. Patients will be randomly assigned to three groups first group(M group) will receive 0.3 mg per kg oral midazolam in 10 ml Dextrose 10% 45 min before surgery )Maximum dose 10mg). Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

Drug: Midazolam group

placebo group (Group C)

PLACEBO COMPARATOR

All patients will be subjected to a thorough medical history, physical examination, routine preoperative investigations will be done to all children including laboratory investigations as (complete blood picture, bleeding time, prothrombin time and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operation room. Parental presence will be allowed throughout sedation and post sedation period. Patients will will receive 10 ml pure oral Dextrose 10% 45 min before surgery. Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

Drug: Control group

Interventions

Melatonin group DRUG

All patients will be subjected to a thorough medical history, physical examination, and routine preoperative investigations will be done to all children, including laboratory investigations (complete blood picture, bleeding time, prothrombin time, and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operating room. Parental presence will be allowed throughout the sedation and post-sedation period. Patients will receive 0.3 mg per kg oral melatonin in 10 ml Dextrose 10% 45 min before surgery (Maximum dose 10mg). Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

Melatonin group (Group M)

Midazolam group DRUG

All patients will be subjected to a thorough medical history, physical examination, and routine preoperative investigations will be done to all children, including laboratory investigations (complete blood picture, bleeding time, prothrombin time, and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operating room. Parental presence will be allowed throughout the sedation and post-sedation period. Patients will receive 0.3 mg per kg oral midazolam in 10 ml Dextrose 10% 45 min before surgery (Maximum dose 10mg). Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

Midazolam group (Group D)

Control group DRUG

All patients will be subjected to a thorough medical history, physical examination, and routine preoperative investigations will be done to all children, including laboratory investigations (complete blood picture, bleeding time, prothrombin time, and partial thromboplastin time). Age, weight, and sex will be recorded. One hour before sedation, children will be transported to an isolated recovery room near the operating room. Parental presence will be allowed throughout the sedation and post-sedation period. Patients will receive 10 ml pure oral Dextrose 10% 45 min before surgery. Assessment of sedation and anxiolysis 30 min after the drug administration using Ramsay sedation scale.

placebo group (Group C)

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• ALL children with ASA class I and class II

You may not qualify if:

• chest infection
• Abnormal mental milestones.
• Children with any organ dysfunction.
• Allergies to any of the drugs used.
• Children with Obstructive sleep apnea.

Sponsors & Collaborators

• Ain Shams University: lead

MeSH Terms

Conditions

Emergence Delirium; Anxiety Disorders

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Delirium; Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Central Study Contacts

Wael sayed El Gharabawy, assisstant professor

CONTACT

+201096973949; gharabawy76@med.asu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: assisstant professor of anesthesia, intensive care, and pain management

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 13, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share