Pharmacogenetic-guided Choice of Post-surgery Analgesics (PRECISE)

Pharmacogenomics (PGx) is the study of how genes affect a person's response to drugs. PGx testing for certain genes can help predict the risk of side effects or therapeutic failure from analgesics. Testing is not regularly performed in clinical practice due to long wait times for results and challenges with integrating test results in the electronic health record. Investigators leading this study hope to find out if providing surgeons with the ability to order a PGx test and electronically receive results with dosing recommendations will increase the use of these tests to guide analgesic choice and improve patient outcomes.

This is a prospective, two-arm randomized implementation study. Eligible participants will be randomly assigned to receive genotype-guided analgesic selection (intervention arm) or usual care (control arm). Both cohorts will undergo pharmacogenetic testing at the time of consenting. The investigators will primarily measure the feasibility of using this test to guide analgesic selection.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Pain; Post Operative Pain
• Intervention / Treatment: Other: Pharmacogenetic testing; Other: Pharmacist note with genotype-guided analgesic recommendations; Other: Pharmacist detailed note with genotype-guided recommendations per CPIC guidelines

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able and willing to provide informed consent
2. Assigned female at birth and aged 18 years or older at the time of study initiation
3. Major gynecologic surgery indicated and planned for hysterectomy, myomectomy, exploratory laparotomy, and open abdominal surgery
4. Willing to provide a buccal swab for PGx testing and comply with all study-related procedures

Exclusion Criteria:

1. Receiving chronic opioid therapy defined as ≥ 3 consecutive months of 1-month prescriptions for an opioid
2. Pregnancy
3. Breastfeeding
4. Treating physician does not want subject to participate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PGx-guided; Pharmacogenetic testing using a 16 gene panel with a pharmacist consult providing genotype-guided recommendations for post-surgery analgesic selection based on CYP2D6 and CYP2C9 results. Pharmacist recommendations for all 16 gene results will also be provided in a detailed note.	Other: Pharmacogenetic testing; Genetic testing of CYP2B6, CYP2C19, CYP2C9, CYP2C cluster CYP2D6, CYP3A5, CYP4F2, DPYD, HLA-A, HLA-B, IFNL4, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1.; Other: Pharmacist note with genotype-guided analgesic recommendations; CYP2C9 normal metabolizers will be recommended to receive ibuprofen and intermediate and poor metabolizers will be recommended to receive naproxen. CYP2D6 normal metabolizers will be recommended to receive tramadol and ultrarapid, intermediate and poor metabolizers will be recommended to receive oxycodone.; Other: Pharmacist detailed note with genotype-guided recommendations per CPIC guidelines; Genotype-guided recommendations for all actionable phenotypes resulted from the 16-gene PGx panel per CPIC guidelines and FDA labeling
Other: Usual care; Pharmacogenetic testing using a 16 gene panel. Post-surgery analgesic selection will be based on usual care (not the PGx results). Pharmacist recommendations for all 16 gene results will be provided in a detailed note with a delayed return of results (30 days post surgery)	Other: Pharmacogenetic testing; Genetic testing of CYP2B6, CYP2C19, CYP2C9, CYP2C cluster CYP2D6, CYP3A5, CYP4F2, DPYD, HLA-A, HLA-B, IFNL4, NUDT15, SLCO1B1, TPMT, UGT1A1, and VKORC1.; Other: Pharmacist detailed note with genotype-guided recommendations per CPIC guidelines; Genotype-guided recommendations for all actionable phenotypes resulted from the 16-gene PGx panel per CPIC guidelines and FDA labeling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of integrating a PGx panel test in the EMR with a pharmacist consult note for each patient	The proportion of PGx test results and pharmacist consult notes returned prior to surgery	14 days
Fidelity to genotype-guided pharmacotherapy recommendations	The proportion of medication selections made in agreement with the genotype-guided dosing recommendations for analgesic medications.	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total opioid consumption in morphine milligram equivalents (MME)	Difference in total MME consumption in variant carriers in PGx-guided group vs. control group	14 days
Acute pain - Self-reported numeric pain score	Mean patient self-reported numeric pain scores (scale: 0-10, 0 = no pain; 10= worst pain imaginable) assessed on POD 0, 3, 7, 14 in the PGx-guided group vs. the control group	14 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Actual): October 31, 2023
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Acute Pain; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Analgesics
• Other Study ID Numbers: 851447

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available upon reasonable request.
• IPD Sharing Time Frame: Study protocol, SAP, ICF will be made available 1 year following enrollment of the last participant. IPD will be made available 6 months after publication of study results
• IPD Sharing Access Criteria: Contact PI, Sony Tuteja, PharmD, sonyt@pennmedicine.upenn.edu with individual requests.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• 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