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CompletedNCT03495388Updated Aug 11, 2025

PG and PK of Oxycodone to Personalize Post-op Pain Management Following Surgery in Children

An observational study in Postoperative Pain and Opioid Dependence, sponsored by Senthil Sadhasivam. Completed at 2 sites in United States. Open to participants aged 8 Years to 18 Years. Per ClinicalTrials.gov, last updated 2025-08-11.

Sponsored by Senthil Sadhasivam · Observational

Study type
Observational
Model
Other
Time perspective
Prospective
Enrollment
129
Ages
8 Years to 18 Years
Sex
All
01

Study summary

Each year, in the U.S. alone, >6 million children undergo painful surgery; up to 50% of them experience significant and serious side effects with opioids and inadequate pain relief. Though 60% of this inter-individual variability in responses results from genetic variations, there is an almost complete lack of understanding of how specific genetic variability affects pain and of the adverse effects of opioids, especially in children. In this project the investigators will focus on oxycodone, a standard and preferred post-surgical oral analgesic in children

The purpose of this research is to study serious immediate and long-term clinical problems from both surgical pain and oxycodone use in children and adolescents to improve the safety and effectiveness of surgical pain relief.

The long-term goals are to improve the safety and effectiveness of surgical pain relief with opioids (a class of drugs/pain relievers) and to minimize the societal burden of disabling Chronic Persistent Surgical Pain (CPSP, which is pain that persists even after the expected healing time from surgery) and Opioid Dependence (OD) by preoperative risk predictions and personalized care with the right dose of the right pain medication for each child.

The overall objective is to determine the impact of risk factors on oxycodone's immediate and long-term negative postoperative outcomes and to personalize dosing in children undergoing outpatient and major inpatient surgery.

Read the detailed description

Research procedures will include:

  1. Pre-operative blood draw for genotyping candidate genes and exploratory genes and for future similar studies will be collected.
  2. Standardized pre-, intra-, and post-operative care will be received by all participants. The study team will record medical history, demographic information, concomitant medications, vitals, pain scores, post-operative nausea and vomiting, and all medications given post-surgery for pain management throughout the participants in-patient stay.
  3. Psychological questionnaires to assess pain, risk of developing OD and chronic pain, anxiety and depression will be administered pre-operatively, and 48-72 hours, 7-14 days, 2 months, 3 months, 6 months and 12 months post-operatively.
  4. Quantitative Sensory Testing will be performed on up to 100 participants pre-operatively, and 48-72 hours,3 months and 12 months post-operatively.
  5. Serial blood draws for oxycodone and methadone pharmacokinetic modeling will be collected from up to 200 participants. QTc measurements will also be recorded from pre- and post-operative EKGs for those participants in which methadone pharmacokinetic blood samples are collected.
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Conditions studied

  • Postoperative Pain
  • Opioid Dependence
03

Who can participate

Ages eligible
8 Years to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Pectus excavatum repair and spinal fusions are two of the most painful surgery children and adolescents undergo. Therefore, the investigators aim to recruit 500 children and adolescents, 8-17.9 years of age, undergoing inpatient pectus excavatum repair or idiopathic scoliosis spinal fusions at Riley Hospital for Children.

Inclusion criteria

  • Boy and girls
  • All races
  • ASA physical status 1 and 2
  • Scheduled for pectus excavatum repair or idiopathic scoliosis spinal fusion
  • Children with OSA will be included but stratified as they have more opioid-related complications.

Exclusion criteria

Exclusion Criteria:

  • Allergy to oxycodone or methadone
  • Developmental delay
  • Neurological disorder
  • Renal or liver disease
  • Pre-operative pain requiring analgesics
  • On inhibitors or inducers of CYP2D6 and CYP3A
  • Cannot read, write and speak English fluently
04

Study design

Observational model
Other
Time perspective
Prospective
Enrollment
129 participants (actual)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • Major Inpatient Surgeries

    Children ages 8-17.9 undergoing pectus excavatum or idiopathic scoliosis spinal fusion at Riley Hospital for Children, who have consented to participate in an observational clinical study as approved by the IU IRB, protocol #1707525204.

    Drug: Oxycodone

Interventions

  • DrugOxycodone

    Post-op pain management medication

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What researchers measure

Primary outcomes

  1. Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects (RD and PONV).

    The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD, and PONV in the immediate post-surgical period (4 days) in the hospital and at home.

    Time frame: Immediately post-surgery during hospital stay and at home up to 1 year post-surgery

  2. Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone.

    The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience poor pain relief in the immediate post-surgical period (4 days) in the hospital and at home.

    Time frame: Immediately post-surgery during hospital stay and at home up to 1 year post-surgery

Secondary outcomes

  1. Look at the impact of CYP2D6 variants on oxycodone's clinical dosing in children to see if specific variants correlate with a need for lower or higher doses of analgesic.

    The investigators will look at CYP2D6 variants to find correlations in oxycodone's PK variability and the need for dose adjustments that lead to desired clinical outcomes in children undergoing major inpatient surgeries.

    Time frame: Pre-operative to post-operative day 2

Other outcomes

  1. Look at genetic oxycodone-related perioperative and bio-psychological factors predisposing children to long-term adverse outcomes such as chronic persistant surgical pain and opioid dependence.

    The investigators will look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with chronic persistent surgical pain and opioid dependence up to 1 year post-surgery. Children will also be asked to complete psychological questionnaires pre-surgery, and at 4 time points post-surgery to assess psycho-psychological factors that may correlate with chronic persistent surgical pain or opioid dependence.

    Time frame: Pre-operative to 12 months post-operative

06

Study locations

2 sites
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • UPMC Children's Hospital
    Pittsburgh, Pennsylvania 15224, United States
07

References and documents

Publications

  • Aruldhas BW, Quinney SK, Packiasabapathy S, Overholser BR, Raymond O, Sivam S, Sivam I, Velu S, Montelibano A, Sadhasivam S. Effects of oxycodone pharmacogenetics on postoperative analgesia and related clinical outcomes in children: a pilot prospective study. Pharmacogenomics. 2023 Mar;24(4):187-197. doi: 10.2217/pgs-2022-0149. Epub 2023 Mar 22. PubMed 36946298 ↗
  • Packiasabapathy S, Aruldhas BW, Zhang P, Overholser BR, Quinney SK, Sadhasivam S. Novel associations between CYP2B6 polymorphisms, perioperative methadone metabolism and clinical outcomes in children. Pharmacogenomics. 2021 Jul;22(10):591-602. doi: 10.2217/pgs-2021-0039. Epub 2021 Jun 8. PubMed 34100292 ↗
  • Sadhasivam S, Aruldhas BW, Packiasabapathy S, Overholser BR, Zhang P, Zang Y, Renschler JS, Fitzgerald RE, Quinney SK. A Novel Perioperative Multidose Methadone-Based Multimodal Analgesic Strategy in Children Achieved Safe and Low Analgesic Blood Methadone Levels Enabling Opioid-Sparing Sustained Analgesia With Minimal Adverse Effects. Anesth Analg. 2021 Aug 1;133(2):327-337. doi: 10.1213/ANE.0000000000005366. PubMed 33481403 ↗

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT03495388
Lead sponsor
Senthil Sadhasivam
Collaborators
Children's Hospital Medical Center, Cincinnati, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Responsible party
Senthil Sadhasivam (Professor, University of Pittsburgh) — Sponsor-investigator
First posted
Apr 12, 2018
Start date
Apr 1, 2018
Primary completion
Jun 15, 2022
Completion
Jun 15, 2022
Last update
Aug 11, 2025

Study contacts

Senthilkumar Sadhasivam, MD, MPH
principal investigator · University of Pittsburgh, UPMC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.

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