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

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ClinicalTrials.gov Identifier: NCT03495388
Recruitment Status : Recruiting
First Posted : April 12, 2018
Last Update Posted : July 28, 2020
Sponsor:
Collaborators:
Children's Hospital Medical Center, Cincinnati
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
Senthilkumar Sadhasivam, MD, MPH, Indiana University

Tracking Information
First Submitted Date March 28, 2018
First Posted Date April 12, 2018
Last Update Posted Date July 28, 2020
Actual Study Start Date April 1, 2018
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: April 4, 2018)
  • Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects (RD and PONV). [ Time Frame: Immediately post-surgery during hospital stay and at home up to 1 year post-surgery ]
    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.
  • Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone. [ Time Frame: Immediately post-surgery during hospital stay and at home up to 1 year post-surgery ]
    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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 4, 2018)
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. [ Time Frame: Pre-operative to post-operative day 2 ]
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.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 4, 2018)
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. [ Time Frame: Pre-operative to 12 months post-operative ]
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title PG and PK of Oxycodone to Personalize Post-op Pain Management Following Surgery in Children
Official Title Pharmacogenetics and Pharmacokinetics of Oxycodone to Personalize Postoperative Pain Management Following Major Inpatient Surgery in Children
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.

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.
Study Type Observational
Study Design Observational Model: Other
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
DNA from blood is obtained and analyzed for genetic variations
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.
Condition
  • Postoperative Pain
  • Opioid Dependence
Intervention Not Provided
Study Groups/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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: April 4, 2018)
500
Original Estimated Enrollment Same as current
Estimated Study Completion Date March 2022
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 8 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Senthilkumar Sadhasivam, MD, MPH (317) 948-3845 ssadhasivam@IUHealth.org
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03495388
Other Study ID Numbers 1707525204
7R01HD089458-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Senthilkumar Sadhasivam, MD, MPH, Indiana University
Study Sponsor Indiana University
Collaborators
  • Children's Hospital Medical Center, Cincinnati
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators
Principal Investigator: Senthilkumar Sadhasivam, MD, MPH Indiana Univeristy
PRS Account Indiana University
Verification Date July 2020