Clinical trial NCT03531268: Prospective Study to Evaluate the Clinical Utility of Perioperative Pharmacogenomic Testing
Official title: Prospective Study to Evaluate the Clinical Utility of Perioperative Pharmacogenomic Testing
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Perioperative/Postoperative Complications
Keywords: Pharmacogenomic Analysis
Clinical Utility
Outcomes
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: CQuentia NGS, LLC
First posted: 2018-05-21
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All subjects meeting inclusion/exclusion criteria will undergo pharmacogenomic testing. The group for which testing is thought to have clinical utility will be compared to the group for which testing is thought to have no clinical utility.
Primary purpose: SCREENING

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical Utility
timeFrame: The day of surgery or the day prior
Secondary outcomes:
measure: Intraoperative and postoperative use of opioids
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Duration times (surgery, anesthesia, length of stay in PACU)
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Pain Assessment
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Postoperative Nausea and Vomiting
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Sedation and Delirium Assessment
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Subject Satisfaction
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Quality of Recovery
timeFrame: 24 hrs +/- 4 hrs after surgery
measure: Length of stay in hospital after surgery
timeFrame: 30 days
measure: Opioid Prescriptions
timeFrame: 30 days
measure: Hospital Readmissions
timeFrame: 30 days
measure: Emergency Room Visits
timeFrame: 30 days
measure: Unscheduled Phone Calls
timeFrame: 30 days
measure: Unscheduled Office Visits
timeFrame: 30 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Srdjan S Nedeljkovic, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.