Perioperative Pharmacogenomic Testing (PPGx)

Perioperative Pharmacogenomic Testing (PPGx) : A Feasibility and Randomised Controlled Pilot Study

This is a single centre, prospective feasibility study and pilot randomised controlled trial of patients scheduled for elective intermediate or major non-cardiac surgery. The investigators plan to randomise up to 200 patients who meet the inclusion criteria to standard care or to personalised perioperative care based on pharmacogenomic testing for drugs commonly used in anaesthesia and postoperative pain management e.g., opioids - morphine, oxycodone and tramadol; anti-emetics - metoclopramide and ondansetron; and non-steroidal drugs - celecoxib and ibuprofen.

The investigators hypothesise that pharmacogenomic testing is feasible prior to elective surgery and through 'personalised prescribing' for precision tailored perioperative care the investigators will improve patient's postoperative quality of recovery, including pain management.

Study Overview

• Status: Recruiting
• Conditions: Anesthesia; Pharmacogenetics
• Intervention / Treatment: Other: Pharmacogenomic optimisation of anaesthetic medications

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michelle D Gerstman, MBBS, MD; Phone Number: +61 3 8559 7681; Email: michelle.gerstman@petermac.org

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
      • Contact: Bernhard Riedel; Email: bernhard.riedel@petermac.org
      • Contact: Michelle Gerstman; Email: michelle.gerstman@petermac.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able to provide written informed consent
2. Age greater than 18 years
3. Elective surgery scheduled greater than 1 week from preoperative assessment and date of pharmacogenomic testing
4. Moderate-Major surgery expecting to last two or more hours with anticipated admission of at least 1 night including: breast, melanoma, colorectal (laparoscopic or open), prostate, or other major surgery (e.g. oesophagectomy, head and neck cancer, retroperitoneal sarcoma, etc.)

Exclusion Criteria:

1. Day case surgery
2. Expected surgery duration of < 2 hours
3. Urgent surgery expected within 1 week of pre-operative assessment
4. Emergency surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pharmacogenomic group; The perioperative (anesthetic and postoperative pain management) plan for each patient will be determined preoperatively by the treating anesthesia team. Thereafter, the pharmacogenomic results of the patient will be released and a personalised anesthetic plan formulated based on international pharmacogenomic guidelines. The treating anesthesia team will then modify the perioperative care plan based on the patients' pharmacogenomic results and the international pharmacogenomic guidelines.	Other: Pharmacogenomic optimisation of anaesthetic medications; Personalisation of anaesthetic plan based on pharmacogenomic results and international guidelines.
No Intervention: Control group; Perioperative care will be managed according to current 'standard care' practice at Peter MacCallum Cancer Centre.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - patient acceptability of pre-operative pharmacogenomic testing prior to their scheduled intermediate-major surgery.	Percentage of eligible patients approached who consent to participate in the study (yes/no).	Pre-consent
Pilot RCT - post-operative pain control on day 1 after surgery	Pain on post-operative day 1 as measured by the Numerical Rating Scale (NRS)	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient pharmacognemic test result availability prior to surgery (i.e. timely test result availability).	Percentage of patient test results available on day of surgery	Time of surgery
Patient perceptions of pharmacogenomic testing and reasons patients decline to participate.	Patient questionnaire regarding patient perceptions of pharmacogenomic testing	Prior to surgery
Actionable genetic variations in our surgical population	Frequency of actionable variations as measured by pharmacogenomic testing	Intraoperative
Frequency of change of drug prescribing based on pharmacogenomic testing	Number of changes during the intraoperative period and post-operative period (pharmacogenomic group).	72 hours
Anesthesia team perceived benefit of modifying perioperative drug choice based on pharmacogenomic results (pharmacogenomic group)	Percentage of anesthetists who select "I found the pharmacogenomic results helpful in prescribing".	72 hours
Post-operative pain and nausea and vomiting	Percentage recovery of the nociceptive domain of the PostopQRS™ scale between groups	30 days
Quality of recovery during the postoperative period	Percentage recovery over time of all domains of the PostopQRS™.	30 days
Post-operative pain as measured by total opioid dose	Total opioid dose used within the peri-operative period intra-operative, 0-24, 24-48 & 48-72 hours after surgery.	72 hours
Quality of life at post-operative day 30	EQ-5D-5L on POD-30 and Days alive at home within 30 days after surgery (DAH-30).	30 days
Quality of recovery on day 1 postoperatively	QoR-15	Day 1

Collaborators and Investigators

• Sponsor: Peter MacCallum Cancer Centre, Australia
• Collaborators: University of Adelaide

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): July 1, 2024

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): May 23, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacogenomics; Postoperative pain; Quality of recovery; Drug metabolism; Individualised care
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: PeterMac ID 20/85

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