Oral Oxycodone for Pediatric Post-Surgical Pain

Overseen By Rachel Bernier, BS, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 4

Sponsor: Boston Children's Hospital

Must not be taking: CYP3A4 inhibitors, CYP2D6 inhibitors

Disqualifiers: Allergy to oxycodone, Sleep apnea, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: Single dose administration

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how children's bodies process oxycodone, a pain medication, after surgery. Researchers seek to learn more about the drug's absorption and metabolism, particularly since some children might experience side effects due to their genetic makeup. The trial involves administering oxycodone through a tube in the stomach during surgery and monitoring its breakdown and use by the body. Children aged 0-6 who are generally healthy, have not used opioids before, and are scheduled for specific surgeries like cleft lip repair or craniotomy may be eligible to participate. As a Phase 4 trial, this research focuses on understanding how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

Participants must stop taking any medications that affect CYP3A4 or CYP2D6, as these can interfere with how oxycodone is processed in the body.

What is the safety track record for oxycodone?

Research has shown that oxycodone is a common pain reliever for both adults and children after surgery. This strong medicine targets specific areas in the brain to ease pain. Oxycodone is usually well-tolerated, but like all opioids, it can have side effects. One study found that its pain-relieving effects are similar to those of another strong painkiller, sulfentanil, used during and after surgery.

However, there are some risks, especially for children. Some children might metabolize oxycodone faster due to their genetics, which could lead to more side effects. Understanding how it works in children's bodies is important.

Additionally, a small number of teenagers who use opioids like oxycodone for surgery might continue using them longer than necessary, which is a concern. Overall, while oxycodone is effective for pain relief, monitoring its use carefully in children is crucial to ensure safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for pediatric post-surgical pain, which often involve intravenous or oral opioids given after surgery, this approach uses oral oxycodone administered via an orogastric tube before surgery begins. This preemptive dosing could potentially manage pain more effectively by addressing it before it fully develops. Researchers are excited about this method because it aligns with standard dosing guidelines while offering a novel timing approach that might reduce the need for additional pain medication after surgery.

What is the effectiveness track record for oxycodone in managing pediatric post-surgical pain?

Research has shown that oxycodone is a strong pain reliever for post-surgical use. Studies have found it effectively reduces pain in both adults and children. Oxycodone affects specific parts of the brain that help control pain. While researchers continue to study its effects in children, it has been used safely in pediatric care. In this trial, participants will receive oral oxycodone through an orogastric tube to manage post-surgical pain. Overall, it is considered safe and effective for this purpose. ^{1 2 6 7 8}

Who Is on the Research Team?

Patcharee Sriswasdi, MD

Principal Investigator

Boston Children Hospital

Are You a Good Fit for This Trial?

This trial is for generally healthy children aged 0-6 who need in-patient surgery like shunt placement, craniotomy, cleft lip/palate repair, or genitourinary surgeries. They shouldn't have taken opioids before and can't join if they have issues with drug absorption/metabolism/excretion, are on certain other meds, allergic to oxycodone, or have breathing problems.

Inclusion Criteria

My child is healthy, hasn't used opioids, and is having specific surgery.

Exclusion Criteria

My child is not on any CYP3A4 or CYP2D6 affecting drugs and has no allergy to oxycodone.

My child does not have sleep apnea or breathing problems.

My child does not have conditions affecting drug processing in their body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose of oral oxycodone via an orogastric tube before surgical incision

Single dose administration

1 visit (in-person)

Pharmacokinetic Sampling

Blood samples are collected at 10 time points to measure serum levels of oxycodone and its metabolites

24 hours

10 blood samples collected

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxycodone

Trial Overview The study is testing how oral oxycodone works in the bodies of pediatric surgical patients at Boston Children's Hospital. It involves giving them oxycodone and then measuring its effects and how it's processed by their bodies. The study also includes genetic tests to see how variations in metabolism genes affect the drug's behavior.

How Is the Trial Designed?

Group I: oral oxycodone Experimental Treatment 1 Intervention

An orogastric tube will be placed in the stomach (placement verified by routine accepted clinical guidelines) under anesthesia as is part of standard routine clinical care to remove gastric contents. The same orogastric tube will be used for intragastric liquid oxycodone administration in a dose of 0.1 mg/kg before the surgical incision. This weight-adjusted dose of 0.1 mg/kg is administered as per standard clinical dosing guidelines at Boston Children's Hospital.

Oxycodone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as OxyContin for:

• Moderate to severe pain
• Chronic pain

Approved in European Union as OxyContin for:

• Severe pain
• Cancer pain

Approved in Canada as OxyContin for:

• Moderate to severe pain

Who Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

In a comprehensive analysis of 1,106 participants across multiple trials, immediate-release (IR) and extended-release (ER) oxycodone/acetaminophen (OC/APAP) demonstrated a safety profile comparable to other low-dose opioid combinations, with no serious adverse events reported in phase 1 trials.

Common adverse events included pruritus, nausea, and dizziness, but these occurred at similar rates to other opioid treatments, indicating that IR/ER OC/APAP is generally well-tolerated among users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials. Barrett, T., Kostenbader, K., Nalamachu, S., et al.[2018]

In a study involving 22 pediatric patients aged 5-14, both oral transmucosal fentanyl citrate (OTFC) and oral oxycodone provided effective pain relief during outpatient burn wound care, with no significant side effects reported.

OTFC was preferred for its better taste, making it a more palatable option for children, while both medications demonstrated similar safety and efficacy profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. Sharar, SR., Carrougher, GJ., Selzer, K., et al.[2019]

Intravenous oxycodone provides adequate postoperative pain relief in pediatric patients, similar to tramadol, but with less sedation and a shorter recovery time in the post-anesthesia care unit (PACU).

Both oxycodone and tramadol had comparable side effects, primarily nausea and vomiting, indicating that oxycodone may be a safer alternative for managing acute postoperative pain in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial. Li, S., Xiong, H., Jia, Y., et al.[2023]

In a study of 79 patients undergoing thumb carpometacarpal arthroplasty or distal radius ORIF, the combination of oxycodone, acetaminophen, and ketorolac showed a trend towards better postoperative pain control and reduced opioid usage compared to other regimens.

Although not statistically significant, the group receiving oxycodone, acetaminophen, and ketorolac experienced fewer complications, suggesting that this combination may enhance safety and efficacy in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-Modal Pain Control in Ambulatory Hand Surgery. Harrison, RK., DiMeo, T., Klinefelter, RD., et al.[2018]

A study of 62 pediatric patients (ages 10-19) showed that controlled-release oxycodone (oxycodone-CR) is safe and effective for managing pain after spinal fusion surgery, with pain scores decreasing from 4.2 to 3.7 out of 10.

Patients transitioned to oxycodone-CR after the immediate postoperative period, using it for an average of 13.3 days, and experienced common side effects like dizziness, constipation, and nausea, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled-release oxycodone for the management of pediatric postoperative pain. Czarnecki, ML., Jandrisevits, MD., Theiler, SC., et al.[2019]

Oxycodone, a commonly used opioid for moderate-to-severe pain, has a higher bioavailability and longer half-life compared to oral morphine, which is important for its effective use in various patient populations.

The pharmacokinetics of oxycodone can vary significantly among individuals, especially in special populations like children and those with liver or renal failure, highlighting the need for careful dosing to maximize pain relief while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of oxycodone. Lugo, RA., Kern, SE.[2022]

Oral prolonged-release oxycodone/naloxone (OXN PR) demonstrated similar pain relief effectiveness as prolonged-release oxycodone (OXY PR) in managing acute postoperative pain for patients after knee surgery, based on a study comparing both medications.

OXN PR not only showed enhanced efficacy and tolerability compared to other opioids during rehabilitation but also significantly improved bowel and bladder function without raising safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged-release oxycodone/naloxone in postoperative pain management: from a randomized clinical trial to usual clinical practice. Kuusniemi, K., Zöllner, J., Sjövall, S., et al.[2017]

The new oxycodone 10-mg/acetaminophen 325-mg formulation (Percocet) was found to be more effective than a higher dose of oxycodone alone in managing acute pain after oral surgery, based on a study of 141 patients.

This combination not only provided faster pain relief but also resulted in fewer treatment-related side effects, highlighting its potential as a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Gammaitoni, AR., Galer, BS., Bulloch, S., et al.[2019]

Oral oxycodone is effective for managing acute postoperative pain, showing superior analgesic efficacy compared to placebo and comparable or better pain relief than intravenous opioids in various surgical procedures, including knee arthroplasty and laparoscopic surgeries.

Patients using oral oxycodone experienced fewer side effects than those on other opioids, did not have prolonged hospital stays, and had lower overall drug costs, making it a safe and reasonable alternative for postoperative pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Oxycodone for Acute Postoperative Pain: A Review of Clinical Trials. Cheung, CW., Ching Wong, SS., Qiu, Q., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06665048?term=AREA%5BInterventionSearch%5D(ROXICODONE)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=3

Evaluating the Analgesic Efficacy of Oxycodone ... The study will assess outcomes such as anesthesia emergence time, extubation time, incidence of emergence agitation, postoperative analgesia, and nausea and ...

2. jeccm.amegroups.org jeccm.amegroups.org/article/view/3661/html

Efficacy and safety of intravenous oxycodone for general ... The pilot study showed that oxycodone was able to provide potent analgesic effects during and after operation, and the effect was comparable to the sulfentanil.

3. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-023-02054-8

Oxycodone vs. tramadol in postoperative parent-controlled ... In this study, we propose that oxycodone-based PCIA can provide postoperative pain relief in pediatric patients effectively and safely.

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK482226/

Oxycodone - StatPearls - NCBI Bookshelf - NIH Oxycodone is a potent semisynthetic opioid agonist prescription medication with agonistic properties on mu-, kappa-, and delta-type opioid receptors.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0885392404000028

Controlled-release oxycodone for the management of ... The results of this study suggest that oxycodone-CR is safe and effective for pediatric patients transitioning to oral analgesics following PCA.

6. publications.aap.org publications.aap.org/pediatrics/article/154/5/e2024068752/199482/Opioid-Prescribing-for-Acute-Pain-Management-in

Opioid Prescribing for Acute Pain Management in Children ... As many as 5% of adolescents who are exposed to opioids for postoperative analgesia may be at risk for persistent opioid use.39 Thus, the CPG ...

7. facs.org facs.org/for-patients/recovering-from-surgery/safe-pain-management/pediatric-pain-control/

Safe and Effective Pain Control After Surgery for Children ... Information on how to provide safe and effective pain control after surgery for children and teens .

8. cdc.gov cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm

CDC Clinical Practice Guideline for Prescribing Opioids ... This guideline provides recommendations for clinicians providing pain care, including those prescribing opioids, for outpatients aged ≥18 years.