Optimization of Pediatric Tonsillectomy to IMprove AnaLgesia (OPTIMAL)

Single-Dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double Blind Clinical Trial

The purpose of this study is to compare the use of short acting opioids (fentanyl/hydromorphone) with long acting opioids (methadone) for pain control following tonsillectomy surgery in children and adolescents.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Tonsillitis; Sleep-Disordered Breathing; Tonsillar Hypertrophy; Pediatric Sleep Apnea
• Intervention / Treatment: Drug: Fentanyl/Hydromorphone; Drug: Methadone

Detailed Description

This is a randomized, double-blind, parallel-group, dose-escalation investigation. Participants ("children" defined as ages 3 - < 12 years and "adolescents" defined as ages 12 - 17 years) will be randomized 2:1 to either methadone or short-acting opioid. Surgical and anesthesia care, except for intraoperative opioid management, are not altered for study purposes. The trial will include 2 periods in 3 parallel age groups. In the first period, each age cohort will recruit 66 patients (44 methadone, 22 control). Children will be randomized to methadone 0.15 mg/kg age-ideal body weight and adolescents to 0.2 mg/kg age-ideal body weight. When an age cohort reaches 66 patients, this is the end of the first period. At that time, an unblinded interim analysis will be conducted in that cohort to determine if dose escalation to 0.2 mg/kg dose in children and the 0.25 mg/kg dose in adolescents are met. Methadone dose escalation will be based on clinically meaningful differences in need for rescue opioid in the PACU and the absence of well-defined opioid adverse events. Outcomes data will be collected in hospital and after discharge. With daily surveys for 7 days, and 3 phone calls on day 30, 3 months and 6 months after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 440
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lisa M Einhorn, MD; Phone Number: 9196814877; Email: lisa.einhorn@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Lisa M. Einhorn, M.D.
      • Contact: Lisa Einhorn; Email: lisa.einhorn@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age >= 3 and < 18 years
2. Elective tonsillectomy +/- adenoidectomy
3. Signed informed consent by parent or legal guardian
4. Children >= 12 years must provide signed written consent, Children >= 7 years must provide verbal assent
5. Negative pregnancy test within 48 hours for post pubescent females

Exclusion Criteria:

1. History of chronic kidney or liver disease
2. Current diagnosis of a chronic pain disorder
3. Planned admission to the Pediatric Intensive Care Unit (PICU)
4. Additional procedures under general anesthesia for which opioids would be prescribed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Short acting opioids: Fentanyl/Hydromorphone; Per Routine Care	Drug: Fentanyl/Hydromorphone; Per routine care, given as needed
Active Comparator: Long acting opioid: Methadone; Initial Dosing: 0.15 mg/kg age-ideal body weight in children age 3 - < 12 years and 0.2 mg/kg age-ideal body weight in adolescents age 12 - 17 years. Dose escalation (possible, based on interim analysis): 0.2 mg/kg age-ideal body weight in children age 3 - < 12 years and 0.25 mg/kg age-ideal body weight in adolescents age 12 - 17 years.	Drug: Methadone; Single-dose intraoperative intravenous methadone with initial dose at 0.15 mg/kg in children and 0.2 mg/kg in adolescents.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who required rescue opioid administration in the PACU (post-anesthesia care unit)	Binary (yes/no) need for opioid in the PACU	Up to 6 hours post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of participant's pain as measured by Numeric Pain Rating Scale	Numeric Pain Rating Scale, 0-10. 0 no pain, 10 worst possible pain	Up to 7 days post surgery
Total amount of opioid medication administered	Postoperative opioid use expressed in morphine milligram equivalents per kilogram	Up to 7 days post surgery
Opioid administration in the PACU (post-anesthesia care unit)	Postoperative opioid use in the recovery room expressed in morphine milligram equivalents per kilogram	Up to 6 hours post surgery
Opioid administration post PACU (post-anesthesia care unit)	Postoperative opioid use after PACU discharge expressed in morphine milligram equivalents per kilogram	Up to 7 days post surgery
Number of participants with adverse event in the PACU (post-anesthesia care unit)	Adverse events will only include those that are determined to be related to the study drugs.	Up to 6 hours post surgery

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Lisa M. Einhorn, MD, Duke University

Publications and helpful links

General Publications

• Einhorn LM, Hoang J, La JO, Kharasch ED. Single-dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double-blind Clinical Trial. Anesthesiology. 2024 Sep 1;141(3):463-474. doi: 10.1097/ALN.0000000000005031.

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: August 27, 2024
• First Posted (Actual): August 29, 2024

Study Record Updates

• Last Update Posted (Actual): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Opioid; Methadone; Tonsillectomy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Stomatognathic Diseases; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Otorhinolaryngologic Diseases; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Pharyngeal Diseases; Pharyngitis; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Sleep Apnea Syndromes; Tonsillitis; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Piperidines; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Ketones; Fentanyl; Hydromorphone; Methadone
• Other Study ID Numbers: Pro00114677; 1R01HD114678-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared in the NICHD DASH repository.
• IPD Sharing Time Frame: Per NIH guidelines. Data will be available indefinitely.
• IPD Sharing Access Criteria: NICHD DASH
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes