Personalized Post-Operative Pain Management

Personalized Post-Operative Opiate Prescriptions Based on Pharmacogenetics of CytochromeP450, COMT, and OPRM1

The main questions this study aims to answer are:

Does perioperative PGx personalized opiate therapy reduce persistent post-operative opioid use dependency, improve pain management and reduce opiate related adverse events in opioid naïve patients after surgery?

Participants will:

Take hydromorphone if the PGx results determine they have a SNP indicating high or low metabolic activity in the CYP2D6 enzyme.

Complete a 7-day pain diary post-discharge. Complete a follow-up phone call once per month for 90 days.

Study Overview

• Status: Active, not recruiting
• Conditions: Post-surgical Pain; Persistent Post Operative Opioid Use
• Intervention / Treatment: Other: PGx guided personalized post-operative pain management; Drug: Oxycodone; Drug: Hydromorphone

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • The University of Tennessee Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1.18-85 years of age 2.Able to read and understand study procedures. 3.Willing to participate and sign an ICF. 4.Opioid naïve 90 days prior to surgery.

Exclusion Criteria:

1. <18 years of age and >85 years of age
2. Unable to understand study procedures.
3. Unwilling to give consent.
4. Patients with cognitive impairment that can affect their ability to give consent.
5. Previous Surgery <14 days from time of enrollment.
6. Allergies to study intervention or oxycodone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard post-operative pain management (control); Patients in the control groups will follow the current hospital standard of care and receive oxycodone 5mg every 4 hours as needed for moderate pain and oxycodone 10mg every four hours as needed for severe pain.	Other: PGx guided personalized post-operative pain management; Patients in the intervention group will receive post operative opioid therapy based on their pharmacogenomic results. Patients who are poor CYP2D6 metabolizers or rapid CYP2D6 metabolizers with moderate or severe pain, will be prescribed either oral hydromorphone 2mg every 4 hours as needed or oral hydromorphone 4mg every 4 hours as needed, respectively. Patients who are intermediate or normal CYP2D6 metabolizers with moderate or severe pain will receive oxycodone 5mg or oxycodone 10mg every 4 hours as needed respectively similar to the treatment offered to the control subjects. Normal or intermediate CYP2D6 metabolizers who are concomitantly taking a drug which is a strong CYP2D6 inducer will be treated as if they are in the rapid metabolizer group, and normal or intermediate patients that are concomitantly taking a drug which is a strong CYP2D6 inhibitor will be treated as if they were a poor metabolizer.; Drug: Oxycodone; oxycodone
Experimental: Pharmacogenomics (PGx) guided treatment (hydromorphone); Patients who are poor CYP2D6 metabolizers or rapid CYP2D6 metabolizers with moderate or severe pain, will be prescribed either oral hydromorphone 2mg every 4 hours as needed or oral hydromorphone 4mg every 4 hours as needed, respectively.	Other: PGx guided personalized post-operative pain management; Patients in the intervention group will receive post operative opioid therapy based on their pharmacogenomic results. Patients who are poor CYP2D6 metabolizers or rapid CYP2D6 metabolizers with moderate or severe pain, will be prescribed either oral hydromorphone 2mg every 4 hours as needed or oral hydromorphone 4mg every 4 hours as needed, respectively. Patients who are intermediate or normal CYP2D6 metabolizers with moderate or severe pain will receive oxycodone 5mg or oxycodone 10mg every 4 hours as needed respectively similar to the treatment offered to the control subjects. Normal or intermediate CYP2D6 metabolizers who are concomitantly taking a drug which is a strong CYP2D6 inducer will be treated as if they are in the rapid metabolizer group, and normal or intermediate patients that are concomitantly taking a drug which is a strong CYP2D6 inhibitor will be treated as if they were a poor metabolizer.; Drug: Hydromorphone; hydromorphone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Persistent Post-Operative Opioid Use	To determine the overall difference in the number of post-operative opioid prescriptions in 90 days using PGx guided post operative medication	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-Surgical Pain	To determine if PGx guided medication improves post-operative pain scores compared to similar patients who are given the standard current post operative opiate treatment. The scores are being rated using the Face, Legs, Activity, Cry and Consolability scale ranging from a minimum value of 0 to a maximum value of 10.	7 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Related Adverse Events	To determine if PGx guided medication reduces total opioid related adverse events compared to standard post operative opiate therapy.	90 days

Collaborators and Investigators

• Sponsor: University of Tennessee Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Estimated): November 1, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacogenomics; CYP2D6 SNPs; OPRM1 SNPs; COMT SNPs
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Hydromorphone; Oxycodone
• Other Study ID Numbers: 5226; CORNET Award (Other Grant/Funding Number: The University of Tennessee Graduate School of Medicine)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No