Precision Opioid Care After Cesarean Delivery (PRECISE-CD)

Study Overview
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Brief Summary
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The purpose of this research is to study serious clinical problems from surgical pain and the use of oxycodone or other opioids in women having a Cesarean Delivery to improve the safety and efficacy of surgical pain relief. This research will ultimately improve the safety and efficacy of surgical pain relief with opioids by preoperative risk predictions and personalized care with the right dose of the right analgesic for each patient.

Detailed Description
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The overall objective is to determine the impact of risk factors on oxycodone and other opioid's adverse postoperative outcomes and to personalize dosing in women having a Cesarean Delivery. For the purpose of this study, immediate adverse postoperative outcomes are characterized as Respiratory Depression (RD), Postoperative Nausea and Vomiting (PONV), and inadequate surgical pain relief. Long-term adverse postoperative outcomes are characterized as Chronic Persistent Surgical Pain (CPSP) and Opioid Dependence (OD). The central hypothesis is that specific genetic factors in pain-opioid pathways significantly impact oxycodone and opioid dosing, analgesia, immediate adverse effects (RD and PONV), and long-term adverse outcomes (CPSP and OD). The aims of this project are to validate genetic variants and to develop a test for preoperative risk prediction in lactating mothers and breastfed babies following cesarean delivery (CD). There is an urgent and unmet critical need for reliable technology to improve safety and effectiveness of opioid use in special populations. Aim 1. Validate and identify genetic risk factors associated with postoperative opioid adverse effects, PONV and RD in adult nursing mothers following CD. Investigators hypothesize that with standardized and genotype-blinded perioperative care, specific variants will identify nursing mothers at risk for opioid-induced RD and PONV (primary outcome), OD and severe pain following CD. In addition, genetic variants will identify risk for opioid-induced sedation and adverse effects in breastfed infants. In addition to clinical outcomes, the investigators will collect post-CD cost of care including length of stay. Aim 2. Develop a laboratory-developed test (LDT) at University of Pittsburgh Genome Center (UGC) for preoperative genetic risk prediction and decision support for surgical patients to prevent adverse opioid outcomes. Investigators will develop a minimum viable product (MVP) (CPT code: 81227), a refined multi-gene panel in UGC's CLIA certified laboratory with a robust combinatorial pharmacogenetic decision support to personalize surgical analgesia with precise opioid use in children and adults, and to prevent RD, PONV, CPSP and OD.

Official Title
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Avoiding Adverse Opioid Outcomes With Proactive Precision Care Following Cesarean Delivery

Conditions
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Cesarean Section Complications, Opioid Use

Intervention / Treatment
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* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant Adult women (>18 y) and their infants All races ASA physical status 2 to 3 Cesarean delivery at UPMC Magee Planned breast feeding mothers and their infants Exclusion Criteria: Serious illnesses or condition of either mother or infant precluding ability to participate in study procedures Multiple gestation pregnancies Preoperative severe pain and opioid use/misuse Allergy to oxycodone Women with opioid use disorder Any known condition that anticipates neonatal observation in NICU immediately after birth General anesthesia anticipated or converted intraoperatively Expected non-viable current gestation or serious neonatal health comorbidities anticipated prior to delivery Severe neurological disorder: any known untreated or uncontrolled seizure disorder, pre-eclampsia with severe features, pre-eclampsia requiring magnesium, elevated ICP other than benign intracranial hypertension condition, or conditions at the discretion of PI Liver disease: any known abnormal live function tests, or conditions at the discretion of PI Renal diseases: any chronic or acute renal insufficiency, or pre-eclampsia diagnosis with abnormal renal function i.e.: severe features, or conditions at the discretion of PI. Contraindications to neuraxial anesthesia, neuraxial morphine, acetaminophen, or NSAIDs which are standard parts of post-cesarean multimodal analgesia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MATERNAL cohort<br>Nursing mothers who underwent Cesarean Delivery and who are receiving oxycodone to treat post-operative pain | Drug: Oxycodone<br>* exposure to opioids after Cesarean Section<br>* Other names: Opioid Exposure;|
| NEONATE-INFANT cohort<br>Neonate encompasses a newborn from the age of birth until <28 days of life. Infant refers to the period of 28 days of life until 1 year of life. | Drug: Oxycodone<br>* exposure to opioids after Cesarean Section<br>* Other names: Opioid Exposure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Opioid-Induced Adverse Effects-PROPORTION of maternal participants with RD | Respiratory depression (RD) measured as Yes or No in occurrence. | From time of surgery to time of discharge up to 3 days post-surgery | 
| Opioid-Induced Adverse Effects-PROPORTION of maternal participants with PONV | Postoperative Nausea and Vomiting (PONV) Intensity Scale. Participants will be categorized as Clinically relevant (Yes) or Not clinically relevant (No) Nausea and Vomiting from the PONV scale. Clinically important PONV is defined as a total score >50 at any time throughout the study period. | From time of surgery to time of discharge up to 3 days post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal Post-operative Pain Scores | Numerical Rating Scale (NRS). The pain scale is from 0 to 10, 0 being no pain and 10 being the worst pain imaginable | From time of delivery to 12-month post-surgery | 
| Total Maternal Inpatient Opioid Use | measured in milligrams of Morphine Equivalents | From time of surgery to discharge-- up to 3 days post-surgery | 
| Extended Hospital Length of Stay-Maternal | Yes/No Proportion of Women discharged beyond 72-hours post-surgery | From surgery to 72 hours postoperation | 
| Length of prescribed opioid use (For Mothers; in days) | Number of days patients take opioids post-surgery. | From day of surgery to 12-month post-surgery | 
| Neonatal Sedation-- PROPORTION of infants with Sedation | Defined as YES (any sleeping > 4 hours in hospital or first week of life) or NO (sleeping) less than 4 hours at a time. | From birth to 7-days post-birth | 
| Neonatal Respiratory Depression--PROPORTION of neonates diagnosed with RD | Yes/No Yes: Defined as respiratory rate 8 or fewer breaths per minute | From birth to time of discharge (up to 3 days post-birth) | 
| Extended Hospital Length of Stay-Neonate | Yes/No Proportion of neonates staying in hospital longer than 72-hours (Yes) | From time of delivery to 72-hours post-delivery | 
| Neonatal Limpness (reporting limpness > 0, or not limp =0) | Proportion of Infants with Limpness reported | From birth to 72-hours post-delivery | 
| Proportion of Neonates Exhibiting opioid withdrawal | SOWSS Sophia Observation Withdrawal Symptoms-Scale; Yes (withdrawal symptoms (scores >4)/No (withdrawal symptoms < 4) | Birth to 3-days postpartum (or discharge from hospital) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Personalized Care