Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section

Study Overview
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Brief Summary
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The purpose of this collaborative CTSA (Clinical and Translational Science Award) application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids in breastfeeding mothers and their infants

Detailed Description
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The approach includes 1) development and implementation of an innovative PPAP infrastructure at participating CTSA hubs (Aim 1) and 2) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids and precision dosing in nursing mothers and infants (Aim 2). SPECIFIC AIMS: The purpose of this collaborative CTSA application is to develop an innovative perioperative precision analgesia platform (PPAP) to improve analgesia and reduce serious immediate and long-term adverse outcomes of perioperative opioids in Aim 1. Develop and implement a perioperative precision analgesia platform (PPAP) by linking genomics to opioid metabolism, Clinical Pharmacogenetics Implementation (CPIC) guidelines, precision dosing, clinical safety, and personalizing analgesia Aim 2. Evaluate utility of PPAP in nursing mothers and their newborns following Cesarean Section The investigators hypothesize that CYP2D6 and other (ABCB1, and OPRM1) variants will explain clinical and pharmacokinetic variations of oxycodone, and PPAP implementation will reduce adverse effects in mothers and infants.

Official Title
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Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section

Conditions
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Cesarean Section Complications, Opioid Use

Intervention / Treatment
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* Diagnostic Test: Preoperative Genotyping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult women (>18 yr) All races American Society of Anesthesiologists Classification (ASA) physical status: 1 to 3 undergoing elective Cesarean section that are willing to receive in-patient opioids. Exclusion Criteria: Health conditions including uncontrolled diabetes (gestational or pre-existing) or hypertension (pre-eclampsia, eclampsia, or chronic) Any history of opioid misuse before or during pregnancy-per self-report and clinical notes Preoperative severe pain and opioid use/misuse, allergy to oxycodone Allergy to oxycodone Significant neurological disorders, liver and renal diseases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Interventional study with mother undergoing elective c-section and the infant
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mother undergoing planned Cesarean section<br>Mother subject will have genotyping blood draw performed at the time of controlled delivery (CD). Blood samples and breast milk samples will also be taken during the oxycodone dosing schedule. | Diagnostic Test: Preoperative Genotyping<br>* Genotype based risk prediction and personalized pain management<br>|
| Experimental: Infant<br>Infant subject will have genotyping blood draw performed only at the time of controlled delivery (CD) | Diagnostic Test: Preoperative Genotyping<br>* Genotype based risk prediction and personalized pain management<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Look at genetic factors predisposing patients to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with patients who experience RD and PONV in the immediate post-surgical period (4 days) in the hospital | Immediately post-surgery during hospital stay | 
| Look at genetic factors predisposing patients to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with patients who experience RD and PONV in the post-surgical period at home up to 1-year | At home up to 1 year post-surgery | 
| Look at genetic factors predisposing patients to inadequate surgical pain relief with oxycodone | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with patients who experience poor pain relief in the immediate post-surgical period (4 days) in the hospital. Poor pain relief will be measured using the Numerical Rating Scale (NRS), which runs on a 0-10 scale; 0 being no pain at all, 10 being the worst pain imaginable. | Immediately post-surgery during hospital stay | 
| Look at genetic factors predisposing patients to inadequate surgical pain relief with oxycodone | The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with patients who experience poor pain relief in the post-surgical period at home up to 1-year. Poor pain relief will be measured using the Numerical Rating Scale (NRS), which runs on a 0-10 scale; 0 being no pain at all, 10 being the worst pain imaginable. | At home up to 1 year post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Look at the impact of CYP2D6 variants on oxycodone's clinical dosing in patients to see if specific variants correlate with a need for lower or higher doses of analgesic. | The investigators will look at CYP2D6 variants to find correlations in oxycodone's PK sampling and the need for dose adjustments that lead to desired clinical outcomes in women undergoing a cesarean section and their infant. | Pre-operative to post-operative day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opioid Exposure