Perioperative Pharmacogenomic Testing

Study Overview
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Brief Summary
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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.

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

Conditions
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Pharmacogenetics, Anesthesia

Intervention / Treatment
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* Other: Pharmacogenomic optimisation of anaesthetic medications


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent Age greater than 18 years Elective surgery scheduled greater than 1 week from preoperative assessment and date of pharmacogenomic testing 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: Day case surgery Expected surgery duration of < 2 hours Urgent surgery expected within 1 week of pre-operative assessment Emergency surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacogenomic group<br>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<br>* Personalisation of anaesthetic plan based on pharmacogenomic results and international guidelines.<br>|
| No Intervention: Control group<br>Perioperative care will be managed according to current 'standard care' practice at Peter MacCallum Cancer Centre. | |

What is the study measuring?
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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 | 
| Quality of recovery on day 1 postoperatively | QoR-15 | Day 1 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug metabolism, Pharmacogenomics, Individualised care, Postoperative pain, Quality of recovery