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

Trial Summary

What is the purpose of this trial?

Oxycodone is an oral opioid analgesic that is most commonly prescribed for the management of pain in post-operative patients at Boston Children's Hospital. Oxycodone has been widely used in adults and children to relieve post-operative pain. However, its pharmacokinetics (what it does in the body) and pharmacodynamics (how it works) have not been well established in children. Some children, because of their specific genetic make-up, may metabolize the drug more quickly and therefore may be at risk for more side effects in the commonly prescribed dose. We would like to find out more about how this drug is absorbed, metabolized and excreted in children. In order to study these aspects, we would like to give oxycodone to surgical patients at Boston Children's Hospital then measure its metabolic activity and also perform a genetic analysis. The genetic testing is specifically to analyze the following genotypes only: cytochrome P450 2D6 (CYP2D6) and cytochrome P450 3A4 (CYP3A4), which represent the differences in cytochrome P450 metabolism of oxycodone.

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 data supports the effectiveness of the drug oxycodone for pediatric post-surgical pain?

Research shows that oral oxycodone is effective for managing acute postoperative pain, and studies have found it to be safe and effective for pain relief in children during outpatient wound care. Additionally, oxycodone combined with acetaminophen has been shown to provide enhanced pain relief compared to oxycodone alone in postsurgical settings. ^{1 2 3 4 5}

Is oral oxycodone safe for children after surgery?

Studies show that controlled-release oxycodone is generally safe for children after surgery, with common side effects like dizziness, constipation, and nausea. It has been used safely in pediatric patients for managing pain after spinal fusion surgery. ^{2 3 5 6 7}

How is the drug oxycodone unique for treating pediatric post-surgical pain?

Oxycodone is unique because it is an opioid that provides effective pain relief with a higher bioavailability (the amount of drug that enters the bloodstream) compared to morphine, and it is metabolized differently, which can be beneficial for children and those with liver or kidney issues. ^{1 3 5 8 9}

Research Team

Patcharee Sriswasdi, MD

Principal Investigator

Boston Children Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Multi-Modal Pain Control in Ambulatory Hand Surgery. [2018]

2. England 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. [2019]

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

Oral Oxycodone for Acute Postoperative Pain: A Review of Clinical Trials. [2018]

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

A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Prolonged-release oxycodone/naloxone in postoperative pain management: from a randomized clinical trial to usual clinical practice. [2017]

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

Controlled-release oxycodone for the management of pediatric postoperative pain. [2019]

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

Safety and Tolerability of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials. [2018]

8. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of oxycodone. [2022]

9. England 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. [2023]