Methadone for Pediatric Tonsillectomy Pain

(OPTIMAL Trial)

Overseen By Lisa M Einhorn, MD

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Disqualifiers: Chronic kidney, liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1 day

440 Participants Needed

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is methadone safe for managing pain in children after tonsillectomy?

The research does not specifically address the safety of methadone for pediatric tonsillectomy pain, but it highlights concerns about opioids like fentanyl and morphine, which can cause side effects such as respiratory depression (slowed breathing) and increased recovery time. These findings suggest caution when using opioids in children after tonsillectomy. ^{1 2 3 4 5}

How does the drug methadone differ from other drugs for managing pain after pediatric tonsillectomy?

Methadone is unique because it is a long-acting opioid, which means it can provide pain relief for a longer period compared to other opioids like fentanyl and morphine that are commonly used for this purpose. This could potentially reduce the frequency of dosing needed to manage pain after tonsillectomy in children. ^{1 2 3 6 7}

Research Team

Lisa M. Einhorn, MD

Principal Investigator

Duke University

Eligibility Criteria

This trial is for children and teens aged 3 to under 18 who need tonsillectomy surgery, with or without adenoidectomy. They must consent (if old enough) and have a parent or guardian's permission. Post-pubescent females need a negative pregnancy test. It excludes those with chronic pain disorders, severe sleep apnea, planned PICU admission after surgery, additional procedures needing opioids, or chronic kidney/liver disease.

Inclusion Criteria

Signed informed consent by parent or legal guardian

I am between 3 and 17 years old.

I am planning to have my tonsils and possibly adenoids removed.

Exclusion Criteria

I have been diagnosed with a chronic pain condition.

I have severe sleep apnea.

My child is scheduled for a stay in the Pediatric Intensive Care Unit.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either methadone or short-acting opioids during tonsillectomy surgery

1 day

1 visit (in-person, surgery day)

Postoperative Monitoring

Participants are monitored for opioid use and adverse events in the PACU

Up to 6 hours post surgery

In-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment with daily surveys for 7 days and follow-up calls

6 months

3 phone calls (day 30, 3 months, 6 months)

Treatment Details

Interventions

• Fentanyl/Hydromorphone
• Methadone

Trial Overview The study compares two types of painkillers for managing post-tonsillectomy pain in kids: Methadone (a long-lasting opioid) versus Fentanyl/Hydromorphone (shorter-acting opioids). The goal is to see which provides better pain control.

Participant Groups

Group I: Short acting opioids: Fentanyl/Hydromorphone Active Control 1 Intervention

Per Routine Care

Group II: Long acting opioid: Methadone Active Control 1 Intervention

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.

Methadone is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Dolophine for:

• Pain management
• Opioid use disorder

Approved in European Union as Methadose for:

• Pain management
• Opioid dependence

Approved in Canada as Physeptone for:

• Pain management
• Opioid use disorder

Approved in Japan as Heptadon for:

• Pain management

Approved in Switzerland as Heptanon for:

• Pain management
• Opioid dependence

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Findings from Research

A study comparing postoperative pain management regimens in children after tonsillectomy and adenoidectomy found no significant differences in length of hospital stay between those receiving a combination of intravenous fentanyl and morphine versus those receiving morphine alone.

Both pain management protocols were effective, but the analysis indicated that the differences in pain relief and other outcomes were trivial and likely not clinically relevant, suggesting that either regimen could be used without impacting recovery time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of opioid analgesic protocols to assessed pain and length of stay in the pediatric postanesthesia unit following tonsillectomy. Smith, J., Newcomb, P., Sundberg, E., et al.[2016]

A standardized, opioid-sparing analgesic protocol significantly reduced opioid prescriptions after pediatric tonsillectomy, decreasing the frequency from 64.9% to 33.5% and opioid use in young children from over 50% to just 2.4%.

The protocol did not compromise patient outcomes, as there was no increase in postoperative returns for pain or other complaints, demonstrating that effective pain management can be achieved with non-opioid medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustaining standardized opioid prescribing practices after pediatric tonsillectomy. Cordray, H., Alfonso, K., Brown, C., et al.[2022]

In a study of 11,578 pediatric patients who underwent tonsillectomy, only 3.5% experienced persistent opioid dispensing, indicating that most children do not require long-term opioid use after the procedure.

The research found that any opioid use in the 30 days following surgery significantly increased the likelihood of continued opioid use later, particularly in patients who had received opioids before surgery or had multiple tonsillectomy procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of dispensed opioids after tonsillectomy in children and adolescents in South Carolina, United States, 2010-2017. Basco, WT., Ward, RC., Taber, DJ., et al.[2021]

In a study of 57 children aged 3-10 undergoing tonsillectomy, a single dose of intravenous morphine significantly reduced immediate postoperative pain, as reported by both the children and their parents, particularly at 30 minutes after awakening from anesthesia.

The use of morphine did not lead to any observed side effects, and children in the morphine group required fewer additional pain medications, indicating its efficacy and safety in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single dose of intraoperative intravenous morphine for analgesia in children undergoing tonsillectomy: Randomized, double-blind clinical trial. de Oliveira Araújo, MC., de Sousa Caixeta, JA., Vilarinho, BF., et al.[2022]

Dexamethasone is commonly used during tonsillectomy to reduce inflammation and pain, which can help improve the postoperative recovery experience for children and decrease the reliance on opioids for pain management.

The review also addresses concerns about the potential link between dexamethasone use and perioperative bleeding, exploring dosing strategies that maximize its benefits while minimizing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of dexamethasone as an adjunct to adenotonsillectomy in the pediatric population. King, A., Elmaraghy, C., Lind, M., et al.[2020]

In a study of 166 children undergoing endoscopic plasma total adenotonsillectomy, preemptive analgesia with a low dose of oxycodone (0.1 mg/kg) significantly reduced postoperative pain compared to standard sufentanil treatment.

The use of preemptive oxycodone resulted in lower serum c-fos levels and better pain management outcomes, as indicated by lower Pediatric Anesthesia Emergence Delirium (PAED) scores and FLACC scores at 24 hours post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone preemptive analgesia after endoscopic plasma total adenotonsillectomy in children: A randomized controlled trial. Wu, J., Gui, Q., Wang, J., et al.[2022]

Dipyrone has been found to provide superior pain relief compared to placebo and is as effective as paracetamol for children undergoing tonsillectomy, based on a systematic review of two randomized clinical trials.

Despite its effectiveness, the limited number of studies and their heterogeneity highlight the need for more rigorous research to fully understand the safety and role of dipyrone in postoperative pain management for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dipyrone as pre-emptive measure in postoperative analgesia after tonsillectomy in children: a systematic review. Stangler, MIS., Lubianca, JPN., Lubianca, JN., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Relationship of opioid analgesic protocols to assessed pain and length of stay in the pediatric postanesthesia unit following tonsillectomy. [2016]

2. Ireland pubmed.ncbi.nlm.nih.gov

Sustaining standardized opioid prescribing practices after pediatric tonsillectomy. [2022]

3. Ireland pubmed.ncbi.nlm.nih.gov

Patterns of dispensed opioids after tonsillectomy in children and adolescents in South Carolina, United States, 2010-2017. [2021]

4. Brazil pubmed.ncbi.nlm.nih.gov

Single dose of intraoperative intravenous morphine for analgesia in children undergoing tonsillectomy: Randomized, double-blind clinical trial. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

A review of dexamethasone as an adjunct to adenotonsillectomy in the pediatric population. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Oxycodone preemptive analgesia after endoscopic plasma total adenotonsillectomy in children: A randomized controlled trial. [2022]

7. Brazil pubmed.ncbi.nlm.nih.gov

Dipyrone as pre-emptive measure in postoperative analgesia after tonsillectomy in children: a systematic review. [2022]