Clinical trial NCT03503292
Conditions: Postoperative Nausea
Keywords: Pharmacogenetics CYP2D6 Ondansetron Granisetron Bariatric surgery
Sponsor: Mayo Clinic
Start date: 2018-05-02; Completion date: 2019-12-30
Enrollment: 92 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The Researchers overall goal is to evaluate the benefit and utility of preemptive genotypic data to guide post-operative nausea and vomiting treatment in the bariatric surgical population. The hypothesis is that using genotypic variation in CYP2D6 to select the appropriate 5HT3 serotonin receptor antagonist to treat PONV will decrease rates of PONV in the bariatric surgical population.

Detailed description:

Arms: arm 1: Participants with CYP2D6 rapid metabolizer status will received granisetron for for post operative nausea and vomiting prophylaxis and treatment arm 2: Participants with CYP2D6 poor or normal metabolizer status will received 4mg ondansetron for post operative nausea and vomiting prophylaxis and treatment
Interventions: intervention 1: Granisetron intervention 2: Ondansetron
Intervention descriptions: intervention 1: Rapid metabolizer will receive 1mg IV Granisetron intervention 2: Poor or normal metabolizers will receive 4mg Ondansetron IV

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Using Pharmacogenomics (PGx) 
results to guide post- 
operative nausea and vomiting 
(PONV) treatment practices: 
A pilot study 
 
NCT03503292 
 
20MAR2018 


 
PONV RFA v.7, DATED 20MAR2018 
Title of the Study:  
 
Using Pharmacogenomics (PGx) results to guide post- 
 
 
 
 
operative nausea and vomiting (PONV) treatment practices: 
 
 
 
 
A pilot study  
 
 
Principal Investigator: 
Yvette Martin, MD PhD  
  
Co-Principal Investigator: Timothy Curry MD, PhD 
 
 
 
 
 
 
 
 
 
 
Co- Investigators: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Coordinators: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Source of Support:  
Center for Individualized Medicine (CIM)   
 
Background 
The incidence of postoperative nausea and vomiting (PONV) in the bariatric surgical population 
can be between 11-22% despite multiple anti-nausea therapies administered. There is the 
potential for substantial morbidity associated with any episode of PONV in the bariatric surgical 
population therefore every attempt must be made to further reduce this adverse anesthetic 
complication [1].  
 
Pharmacogenomics (PGx) is a new field in individualized medicine generally concerned with 
genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and drug targets 
that explain inter-individual variation in drug efficacy and toxicity [2]. 
 
The continued high failure rates of PONV therapy despite multi-therapy approach makes 
genetic polymorphisms in the pharmacokinetic and/or pharmacodynamic pathways of the anti-
nausea agents a likely contributor to the observed failed therapy. Preemptive PGx testing has 
the potential to improve clinical outcomes by using an individual’s genotype to inform 
personalization and optimization of drug therapy [3].  
 
Current anti-nausea management includes five drug classes: 5HT3 antagonists, dopamine 
antagonists, anticholinergics, steroids, and NK-1 receptor antagonists [4,5]. There is a growing 
body of evidence, including our own preliminary studies, that the efficacy of the commonly used 
5HT3 drug ondansetron is influenced by PGx variants in the drug metabolizing enzyme 
CYP2D6 [6.7]. Any patient with a rapid metabolizer CYP2D6 genotype may have reduced 
treatment efficacy because of the rapid elimination of ondansetron. Gransietron is an alternative 


 
PONV RFA v.7, DATED 20MAR2018 
agent within the same 5HT3 antagonist category which is not dependent on the CYP2D6 
genotype that could be selectively used in any patient with a CYP2D6 ultrarapid metabolizer 
genotype. There are no current studies on selecting a specific anti-nausea drug type based on a 
patient’s genetic status for this high risk population. 
 
Genotype specific drug selection requires advance knowledge of a patient’s genotype. Mayo 
Clinic’s Individualized Medicine Clinic (within the Center for Individualized Medicine) has 
established a Pharmacogenomics Testing Service. Though single gene PGx testing has long 
been used at Mayo Clinic, panel tests that cover more genes at a lesser cost than previous 
single gene tests are increasing in availability.  This study, to prospectively evaluate the impact 
of preemptive genome guided pharmacotherapy for PONV in the bariatric surgical population, is 
one of a limited number of pilots offering clinical PGx testing utilizing these panel tests offered 
within the Center for Individualized Medicine. 
 
The clinical value of the testing service offered by CIM and integration of genetic data into the 
clinical decision making process creates the opportunity to improve understanding of the 
influence of genomics on multimodal anti-nausea therapies in this high risk population as well as 
the opportunity to assist anesthesiologists and surgeons improve the medication experience of 
their patients. Patients may also benefit from understanding their own PGx variations and the 
relevance of their results.  
 
Specific aim 
The goal of this study is to examine the current and (potential) future therapeutic relevance of 
PGx testing for bariatric surgical patients in order to improve patient clinical care at Mayo Clinic 
with more effective and efficient prescribing of anti-nausea medications. 
To help accomplish this we will: 
1. Facilitate sample collection and PGx testing;  
2. Review returned patient PGx results, identifying PGx variants associated with current 
anti-nausea therapies; 
3. Provide recommendations to anesthesiologist and surgeons for therapeutic adjustments 
related to the 5HT3 class of anti-nausea medications;  
4. Deliver meaningful information to patients for future prescribing events; 
5. Create a data repository of bariatric surgical patients’ genomic variants and  
corresponding anti-nausea medication adjustment recommendations; 
6. Evaluate pharmacogenomics as a method to reduce PONV rates in the bariatric surgical 
population; 
 
Patient Selection 
To be eligible for this study, the following inclusion and exclusion criteria must be adhered to: 
 
Inclusion Criteria 
 
A Mayo Clinic patient scheduled to undergo any bariatric surgical procedure, including 
Roux-en-Y gastric bypass, sleeve gastrectomy, or duodenal switch.  
 
Patient age 18 or above.  


 
PONV RFA v.7, DATED 20MAR2018 
 
Patients must understand and provide written informed consent prior to initiation of any 
study-specific procedures.  
 
Patient is willing to engage in a medication adjustment as part of their clinical visit (when 
needed). 
 
Exclusion Criteria 
 
Patient with uncontrolled concurrent illness including psychiatric illness, or situations that 
would limit compliance with the study requirements or the ability to willingly give written 
informed consent. 
 
Any patient who will be unable to have genetic testing at minimum of 1 week  prior to 
scheduled surgery or with allergies to ondansetron or granisetron. 
 
Any patient with prior pharmacogenomics testing that is readily available in the medical 
record will be excluded from this study.  
 
Any patient that is pregnant 
 
   
 
Study Design  
We plan to recruit approximately 100 bariatric surgical patients to this study. Patients who have 
met the inclusion and exclusion criteria and who have signed the informed consent will be asked 
to provide a one-time buccal scraping. This sample will be sent to OneOme™ Laboratory for 
use for the CLIA/CAP approved RightMed™ test (PGx gene panel).  
 
Results for the patient will be returned to Mayo Clinic and placed into the patient EHR to be 
utilized for clinical treatment decisions at minimum of one-week prior to surgery. If necessary, to 
assist in interpretation of the PGx test results, a PGx-trained pharmacist will review the test 
report, and document assessment via the e-Consult mechanism. A patient letter based on their 
results may be recommended by the pharmacist on a case-by-case basis. During this process, 
we will document PGx variants, identify “actionable” variants potentially impacting current 
medications and all prescription(s) changes considered.  If indicated due to PGx variants or 
current medication list, the patient may have a face-to-face or virtual visit with a pharmacist to 
discuss their PGx results. If the patient participates in a face-to-face visit with a pharmacist as 
part of standard patient care, medication reconciliation would be performed and the data will be 
collected via interview. 
  
On the day of surgery, the participant will receive either ondansetron or granisetron as the 5HT3 
anti-nausea medication based on their CYP2D6 genotype. All other anti-nausea therapies will 
remain consistent. Medication recommendations and education will be provided to all 
anesthesiologist and surgeons caring for these patients via the EHR.  
 
 
All clinical data (demographics as well as predictor, outcome and confounding data) will be 
collected from the anesthesia exposure database from the Mayo Clinic - Rochester 
Anesthesiology Department. 


 
PONV RFA v.7, DATED 20MAR2018 
  
Patients will be given information and education materials and references about PGx testing as 
appropriate, and will also have access to the lab results report and consult notes via the Mayo 
Clinic Patient Online Services portal. Patients may also request a copy of their results through 
Mayo Clinic Medical Records. 
 
 
Consenting Procedures 
 
Study participants will be identified by the bariatric surgeons participating in this pilot study. A 
member of the research team listed on the IRB will meet with the patient to discuss the study if 
they are eligible. The informed consent document will be used as a guide for this discussion.   
If feasible, the consent documents may be sent in advance for review by potential participants 
and their families. The documents will be accompanied by a letter introducing the study and that 
patient and his/her family will be invited to meet with a member of the research team during one 
of their upcoming appointments to learn more about the study and to go over the  information 
provided in the consent documents. 
 
The study team will provide a paper consent form for signature. A photocopy of the signed 
consent form will be given to the subject for their records.   
 
 
Data Analysis 
The statistical analysis will be largely descriptive. Continuous variables will be summarized 
using descriptive statistics (N, mean, standard deviation, median, minimum and maximum). 
Categorical variables will be presented using frequencies and percentages. Time-to-event 
variables will be described by N, median, range, number censored, and Kaplan-Meier plots. 
 
 
References 
1. 
Weingarten TN, Hawkins NM, Beam WB, et al.: Factors associated with prolonged 
anesthesia recovery following laparoscopic bariatric surgery: a retrospective analysis. 
Obesity surgery. 25:1024-1030, 2015. 
2.    Evans, W.E. and M.V. Relling, Pharmacogenomics: translating functional genomics into 
rational therapeutics. Science, 1999. 286(5439): p. 487-491. 
3.    US Food & Drug Administration, Genomics > Table of Pharmacogenomic Biomarkers in 
Drug Labeling.  11 July 2016.  
http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm08337
8.htm 
4. 
Gan TJ, Diemunsch P, Habib AS, et al.: Consensus guidelines for the management of 
postoperative nausea and vomiting. Anesthesia and analgesia. 118:85-113, 2014. 
5. 
Apfel CC, Korttila K, Abdalla M, et al.: A factorial trial of six interventions for the prevention 
of postoperative nausea and vomiting. The New England journal of medicine. 350:2441-
2451, 2004. 
6. 
Bell GC, Caudle KE, Whirl-Carrillo M, et al.: Clinical Pharmacogenetics Implementation 
Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and 
tropisetron. Clinical pharmacology and therapeutics. 2016. 


 
PONV RFA v.7, DATED 20MAR2018 
7. 
Candiotti KA, Birnbach DJ, Lubarsky DA, et al.: The impact of pharmacogenomics on 
postoperative nausea and vomiting: do CYP2D6 allele copy number and polymorphisms 
affect the success or failure of ondansetron prophylaxis? Anesthesiology. 102:543-549, 
2005.