Prospective Study to Evaluate the Clinical Utility of Perioperative Pharmacogenomic Testing

In the perioperative realm, studies have demonstrated an association of genotype with efficacy of medications applicable to the surgical setting. A clinical association exists between the genotype of various genes and with opioid efficacy and toxicity - specifically for drugs such as oxycodone, codeine, morphine, fentanyl, and tramadol. More studies are needed to assess the effects of personalized dosing of analgesics during the perioperative process for various surgical procedures. The application of Pharmacogenomic testing (PGx) to perioperative medicine is novel, has much potential for growth and may potentially improve outcomes. However, successful implementation of a system to evaluate PGx and integrate results into clinical decision-making is challenging and has not been adequately assessed. The investigators propose to conduct PGx testing for patients undergoing surgery, evaluate its clinical utility, and assess outcomes. The investigators hypothesize that PGx testing may ultimately lead to a decrease in adverse events and improved outcomes in the perioperative period.

Study Overview

• Status: Withdrawn
• Conditions: Perioperative/Postoperative Complications
• Intervention / Treatment: Other: PGx Testing

Detailed Description

Potential subjects will participate in screening with a minimum of 4 days prior to their planned surgery. The study involves obtaining mouth swab samples for genetic testing and employing standardized measures for PGx testing of subjects preoperatively.

Study staff will pre-screen potential subjects scheduled at the preoperative center or on surgeons' operative schedules. The study team member will ask the treating clinician involved with the care of a patient for permission to speak to the patient. The physician or a member of the research staff will describe the study to potentially eligible patients and a study investigator will obtain consent. After meeting inclusion and exclusion criteria, subjects who agree to participate in the study will complete study questionnaires and provide a swab sample for PGx analysis.

Trained members of the research staff will obtain a buccal swab sample from each subject who has given informed consent to participate in study procedures. The buccal swab will be packaged and shipped to an outside laboratory for processing and the conduct of the PGx testing. The results of the PGx testing will be provided in a standardized report and sent back to the research staff conducting the study. Typically, the turn-around for shipping the sample and obtaining the results will be 4 days. The results will be available to the anesthesiologist prior to the patient's surgery.

Prior to the initiation of the scheduled surgery, the anesthesiologist will be asked to complete a questionnaire about the clinical utility of PGx testing for that subject. In the perioperative group of subjects for whom clinicians find clinical utility for PGx testing (experimental group), outcomes will be compared to the remaining subjects (control group) for whom PGx testing was felt not to have any clinical utility.

After surgery, there will be two assessment periods. Clinical outcomes and the quality of the subject's recovery from surgery will be assessed postoperatively at 24 hours +/-4 hours after surgery by directly interviewing each study subject and reviewing the electronic medical record. Additional assessments of subjects will be conducted by review of the electronic medical record at 30 days +/- 3 days postoperatively.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02110
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Adults 18 years of age or older at screening.
2. Adults with qualifying insurance coverage.
3. Subjects scheduled to undergo elective surgery with an expected hospitalization 24 hrs =/- 4 hrs after surgery.
4. American Society of Anesthesiology (ASA) physical status 1, 2, or 3.

5. One or more of the following:

   • Subjects prescribed 4 or more medications at time of surgery.
   • Any subject prescribed any one of the following medication categories: opioid, benzodiazepine, antidepressant, antipsychotic, stimulant, mood stabilizer, NSAIDs, anti-epileptic drugs.
   • Any subject prescribed any one of the following medication categories: antiplatelet therapy, anticoagulant drugs.
6. Able to provide informed consent, adhere to the study protocol, and complete all study assessments.

Exclusion Criteria:

1. Subjects who do not have insurance coverage for PGx testing.
2. Subjects who are expected to have surgery prior to the ability to obtain the results of the pharmacogenomic testing (generally it takes 4 days to obtain the results of testing).
3. Subjects who are not being prescribed 4 or more medications, or who are not receiving any of the medication categories noted in the inclusion criteria.
4. Planned multiple surgical procedures within the 30-day study follow up period.
5. Clinically significant medical or psychiatric disease that, in the opinion of the investigator, would make participation in a clinical study inappropriate. This includes any psychiatric or other disease that would cause the subject to be unable to comply with the study requirements.
6. Administration of an investigational drug within 30 days prior to providing PGx testing, or planned administration of an investigational product during the subject's participation in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PGx testing has clinical utility; These are subjects whose PGx testing is judged to have clinical utility and whose clinical care may be modified. Modifications may include altering doses or types of drugs given based on metabolic profile of the patient.	Other: PGx Testing; Pharmacogenomic (PGx) testing will be administered to all subjects. The results of PGx testing will be evaluated for clinical utility. Subjects will be evaluated based on whether PGx testing has clinical utility or has no clinical utility.
No Intervention: PGx testing has no clinical utility; These are subjects whose PGx testing is judged to have no clinical utility. Care "as usual" is provided, and there are no changes in drug selection or dosing based on the results of PGx testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Utility	The anesthesiologist will be shown the results of PGx testing and will complete a "Clinical Utility Questionnaire" regarding the clinical utility of PGx testing for the subject. The responses will be rated: 0 = no utility; 1 = some utility; 2 = significant utility. The larger value (2) is considered as having a higher utility for this scale.	The day of surgery or the day prior

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative and postoperative use of opioids	The use of intraoperative and postoperative use of opioids will be measured (morphine mg equivalents)	24 hrs +/- 4 hrs after surgery
Duration times (surgery, anesthesia, length of stay in PACU)	Surgical duration and anesthesia duration times, length of stay in PACU (duration will be measured in minutes)	24 hrs +/- 4 hrs after surgery
Pain Assessment	Pain Numeric Rating Scale, 0 - 10 (0 = no pain, 10 = maximum pain) (lower values = better outcome)	24 hrs +/- 4 hrs after surgery
Postoperative Nausea and Vomiting	Postoperative Nausea and Vomiting Scale (0 = no nausea/vomiting, 200 = maximal nausea/vomiting) (lower values = better outcome)	24 hrs +/- 4 hrs after surgery
Sedation and Delirium Assessment	Richmond Agitation and Sedation Scale (-5 = unarousable, 0 = alert and calm, +4 = combative) (values = 0 are best outcome)	24 hrs +/- 4 hrs after surgery
Subject Satisfaction	Subject Satisfaction Questionnaire (1 = extremely dissatisfied, 5 = extremely satisfied) (higher values = best outcome)	24 hrs +/- 4 hrs after surgery
Quality of Recovery	Quality of Recovery Questionnaire (0 = poor, 150 = excellent) (higher values = best outcome)	24 hrs +/- 4 hrs after surgery
Length of stay in hospital after surgery	Length of stay in the hospital after surgery (days)(lower number = best outcome)	30 days
Opioid Prescriptions	Amount of opioids prescribed after surgery (morphine mg equivalents) (lower amount = best outcome)	30 days
Hospital Readmissions	Number of times readmitted to hospital within 30 days after surgery (lower number = best outcome)	30 days
Emergency Room Visits	Number of emergency room visits within 30 days after surgery (lower number = best outcome)	30 days
Unscheduled Phone Calls	Number of unscheduled phone calls to the doctor's office within 30 days after surgery (lower number = best outcome)	30 days
Unscheduled Office Visits	Number of unscheduled visits to the doctor's office within 30 days after surgery (lower number = best outcome)	30 days

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: CQuentia NGS, LLC
• Investigators: Study Director: Srdjan S Nedeljkovic, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Cregg R, Russo G, Gubbay A, Branford R, Sato H. Pharmacogenetics of analgesic drugs. Br J Pain. 2013 Nov;7(4):189-208. doi: 10.1177/2049463713507439.
• Jannetto PJ, Bratanow NC. Utilization of pharmacogenomics and therapeutic drug monitoring for opioid pain management. Pharmacogenomics. 2009 Jul;10(7):1157-67. doi: 10.2217/pgs.09.64.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 20, 2018
• Primary Completion (Anticipated): May 20, 2020
• Study Completion (Anticipated): May 20, 2020

Study Registration Dates

• First Submitted: April 24, 2018
• First Submitted That Met QC Criteria: May 9, 2018
• First Posted (Actual): May 21, 2018

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Outcomes; Clinical Utility; Pharmacogenomic Analysis
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: 2018P000454

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No