Pain, PostoperativePhase 4OPTIMALNCT06576830
Optimization of Pediatric Tonsillectomy to IMprove AnaLgesia
A Phase 4 study testing Methadone and Fentanyl/Hydromorphone in people with Pain, Postoperative and Tonsillar Hypertrophy, run by Duke University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Postoperative, Tonsillar Hypertrophy, Tonsillitis
- What is being tested?
- Methadone and Fentanyl/Hydromorphone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 440 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Nov 2024to 1 Jun 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Age >= 3 and < 18 years
- Elective tonsillectomy +/- adenoidectomy
- Signed informed consent by parent or legal guardian
- Children >= 12 years must provide signed written consent, Children >= 7 years must provide verbal assent
- Negative pregnancy test within 48 hours for post pubescent females
Who cannot join
- History of chronic kidney or liver disease
- Current diagnosis of a chronic pain disorder
- Planned admission to the Pediatric Intensive Care Unit (PICU)
- Additional procedures under general anesthesia for which opioids would be prescribed
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Lisa Einhorn, lisa.einhorn@duke.edu
Lisa M. Einhorn, M.D.
About this study
Official title: 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.
Read the 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.
- Conditions
- Pain, Postoperative, Tonsillar Hypertrophy, Tonsillitis, Pediatric Sleep Apnea, Sleep-Disordered Breathing
- Being tested
- Methadone, Fentanyl/Hydromorphone
- Keywords
- Methadone, Tonsillectomy, Opioid
- Medical subject headings
- Pain, Postoperative, Tonsillitis, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Single-dose intraoperative intravenous methadone with initial dose at 0.15 mg/kg in children and 0.2 mg/kg in adolescents.
Fentanyl/HydromorphoneDrug
Per routine care, given as needed
| Study group | Role | What they receive |
|---|---|---|
| Short acting opioids: Fentanyl/Hydromorphone | Active comparator | Per Routine Care Receives: Drug: Fentanyl/Hydromorphone |
| Long acting opioid: Methadone | Active comparator | 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. Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants who required rescue opioid administration in the PACU (post-anesthesia care unit)
Binary (yes/no) need for opioid in the PACU
Measured: Up to 6 hours post surgery
Secondary outcomes (5)
Total amount of opioid medication administered
Postoperative opioid use expressed in morphine milligram equivalents per kilogram
Measured: 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
Measured: 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
Measured: Up to 7 days post surgery
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
Measured: 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.
Measured: Up to 6 hours post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2024
- Study start21 Nov 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 440 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Lisa M. Einhorn, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06576830
- Sponsor's protocol ID
- Pro00114677
- Other IDs
- 1R01HD114678-01
- Acronym
- OPTIMAL
- Status last verified
- Dec 2025
- First submitted
- 27 Aug 2024
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared in the NICHD DASH repository.
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.
PubMed 38669011
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double Blind Clinical Trial
- ClinicalTrials.gov ID
- NCT06576830
- Acronym / sponsor ID
- OPTIMAL / Pro00114677
- Conditions
- Pain, Postoperative, Tonsillar Hypertrophy, Tonsillitis, Pediatric Sleep Apnea, Sleep-Disordered Breathing
- Keywords
- Methadone, Tonsillectomy, Opioid
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 440 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 21 Nov 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 1 Jun 2029 (estimated)
- First posted
- 29 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Short acting opioids: Fentanyl/Hydromorphone | Active comparator | Drug: Fentanyl/HydromorphonePer Routine Care |
| Long acting opioid: Methadone | Active comparator | Drug: MethadoneInitial 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. |
Who may qualify
- Ages
- 3 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Age >= 3 and < 18 years
- Elective tonsillectomy +/- adenoidectomy
- Signed informed consent by parent or legal guardian
- Children >= 12 years must provide signed written consent, Children >= 7 years must provide verbal assent
- Negative pregnancy test within 48 hours for post pubescent females
Key exclusion criteria (4 listed)
- History of chronic kidney or liver disease
- Current diagnosis of a chronic pain disorder
- Planned admission to the Pediatric Intensive Care Unit (PICU)
- Additional procedures under general anesthesia for which opioids would be prescribed
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneSingle-dose intraoperative intravenous methadone with initial dose at 0.15 mg/kg in children and 0.2 mg/kg in adolescents. | Drug | Long acting opioid: Methadone |
| Fentanyl/HydromorphonePer routine care, given as needed | Drug | Short acting opioids: Fentanyl/Hydromorphone |
Primary outcome
Number of participants who required rescue opioid administration in the PACU (post-anesthesia care unit)
Time frame: Up to 6 hours post surgery
Binary (yes/no) need for opioid in the PACU
5 secondary outcomes
Total amount of opioid medication administered
Time frame: Up to 7 days post surgery
Opioid administration in the PACU (post-anesthesia care unit)
Time frame: Up to 6 hours post surgery
Opioid administration post PACU (post-anesthesia care unit)
Time frame: Up to 7 days post surgery
Evaluation of participant's pain as measured by Numeric Pain Rating Scale
Time frame: Up to 7 days post surgery
Number of participants with adverse event in the PACU (post-anesthesia care unit)
Time frame: Up to 6 hours post surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Background: PubMed 38669011Einhorn 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.
- Individual participant dataSharing planned: Yes. Data will be shared in the NICHD DASH repository.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Lisa M. Einhorn, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone and Fentanyl/Hydromorphone in people with Pain, Postoperative and Tonsillar Hypertrophy, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lisa M Einhorn, MD (9196814877, lisa.einhorn@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who required rescue opioid administration in the PACU (post-anesthesia care unit) (time frame: Up to 6 hours post surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06576830, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.