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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on finding the best way to manage pain in children and teens after tonsil removal surgery. It compares the effectiveness of short-acting opioids like fentanyl and hydromorphone with the long-acting opioid methadone to determine which provides better pain relief after the procedure. The study seeks participants aged 3 to 17 who are scheduled for a tonsillectomy, with or without adenoid removal, and who do not have a history of chronic kidney or liver disease or chronic pain disorders. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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.

What is the safety track record for these treatments?

Research shows that methadone, a long-lasting pain medication, has been used successfully in major surgeries for children. However, limited information exists about its use in children undergoing tonsil removal. Studies on pain management for this surgery indicate that methadone has not been widely researched for this purpose.

In other surgeries, a single dose of methadone has reduced the need for additional pain medication, suggesting potential benefits for pain relief. However, insufficient information exists about the safety of methadone for children having their tonsils removed, making it crucial to weigh the potential benefits and risks carefully.

The same trial compares other pain medications like fentanyl and hydromorphone, which are more commonly used for tonsil removal and have more safety information available.

Overall, while methadone seems promising, more research is needed to confirm its safety for tonsil removal in children. Participants should consult their healthcare providers to understand what this means for them. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for pediatric tonsillectomy pain, which typically involve short-acting opioids like fentanyl or hydromorphone, methadone offers a long-acting alternative. Methadone's extended duration of action could mean fewer doses are needed throughout the day, potentially improving pain management and convenience for both kids and caregivers. Researchers are excited about methadone because it may provide more consistent pain relief, reducing the peaks and troughs associated with short-acting opioids, and could minimize the risk of developing opioid tolerance.

What evidence suggests that this trial's treatments could be effective for pediatric tonsillectomy pain?

Research has shown that methadone, studied in this trial, can help manage pain in children after a tonsillectomy. One study found that children who received a single dose of methadone during surgery needed fewer additional pain medications in the following week. This suggests methadone provides longer-lasting pain relief compared to short-acting painkillers like fentanyl or hydromorphone, which are also studied in this trial as a separate treatment arm. Methadone's longer duration may reduce the need for frequent doses, aiding recovery. Overall, these findings support methadone as a promising option for better pain management in children undergoing tonsillectomies. ^{1 2 6 7 8}

Who Is on the Research Team?

Lisa M. Einhorn, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38669011/

Single-dose Intraoperative Methadone for Pain Management ... This small initial study in children undergoing tonsillectomy found that single-dose intraoperative methadone at 0.15 mg/kg age ideal body weight was opioid- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11321919/

Single-Dose Intraoperative Methadone for Pain ... This study found that patients who received a single intraoperative dose of methadone 0.15 mg/kg age-ideal body weight required less opioid in the first week ...

3. www2.pedsanesthesia.org www2.pedsanesthesia.org/meetings/2024winter/guide/posters/uploads/247--PR1-160.pdf

Single-Dose Intraoperative Methadone for Pain Management ... Hypothesis: Single-dose methadone would result in less 7-day postoperative opioid use compared with as-needed short-duration opioids in pediatric tonsillectomy ...

4. anesthesiology.duke.edu anesthesiology.duke.edu/news/revolutionizing-pediatric-tonsillectomy-therapeutics

Revolutionizing Pediatric Tonsillectomy Therapeutics A fully powered randomized controlled trial using IV methadone in almost 400 children undergoing tonsillectomy with the goal to analyze both efficacy and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06576830

Optimization of Pediatric Tonsillectomy to IMprove AnaLgesia 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 ...

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/26/NCT05244226/Prot_SAP_000.pdf

A Randomized Double Blind Methadone Pilot Study ... Methadone has been used in major pediatric surgeries with encouraging results, but it has not been studied in pediatric tonsillectomy. Our central hypothesis is ...

7. joma.amegroups.org joma.amegroups.org/article/view/7304/html

Analgesia for adenotonsillectomy in pediatric patients In conclusion, evidence strongly supports NSAIDs for post-tonsillectomy pain control, with ibuprofen having the most favorable safety profile, ...

8. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/pan.15009

The effect of intraoperative methadone on postoperative ... A single dose of intraoperative methadone reduces short-term postoperative opioid requirements in children after orchiopexy for nondescended testes.