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

Senthil Sadhasivam

Status: Completed

Conditions: Postoperative Pain; Opioid Dependence

Treatments: Drug: Oxycodone

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT03495388

7R01HD089458-02 (U.S. NIH Grant/Contract)

STUDY21070170

Details and patient eligibility

About

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.

Full 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.

Enrollment: 129 patients

Sex: All

Ages: 8 to 18 years old

Volunteers: No Healthy Volunteers

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

• 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

Trial design

129 participants in 1 patient group

Major Inpatient Surgeries

Description:

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.

Treatment:

Drug: Oxycodone