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

NCT03495388 | Completed FDA Drug

• 2 other identifiers: STUDY210701707R01HD089458-02
• Study Type: observational
• Target: 129
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Postoperative Pain; Opioid Dependence

Outcome Measures

Primary Outcomes (2)

• 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.

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

• 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.

  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.

  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.

  Pre-operative to 12 months post-operative

Study Arms (1)

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

Oxycodone DRUG

Post-op pain management medication

Major Inpatient Surgeries

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Senthil Sadhasivam: lead
• Children's Hospital Medical Center, Cincinnati: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

UPMC Children's Hospital

Pittsburgh, Pennsylvania, 15224, United States

Location

Related Publications (3)

• 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.

  PMID: 36946298 DERIVED

• 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.

  PMID: 34100292 DERIVED

• 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.

  PMID: 33481403 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA from blood is obtained and analyzed for genetic variations

MeSH Terms

Conditions

Pain, Postoperative; Opioid-Related Disorders

Interventions

Oxycodone

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Senthilkumar Sadhasivam, MD, MPH

  University of Pittsburgh, UPMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: April 12, 2018
• Study Start: April 1, 2018
• Primary Completion: June 15, 2022
• Study Completion: June 15, 2022
• Last Updated: August 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)