Precision Opioid Care After Cesarean Delivery (PRECISE-CD) (PRECISE-CD)

Avoiding Adverse Opioid Outcomes With Proactive Precision Care Following Cesarean Delivery

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.

Study Overview

• Status: Completed
• Conditions: Cesarean Section Complications; Opioid Use
• Intervention / Treatment: Drug: Oxycodone

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 341

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Women's Hospital of UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Participants who have Cesarean Delivery and who plan to breast feed their infants

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MATERNAL cohort; Nursing mothers who underwent Cesarean Delivery and who are receiving oxycodone to treat post-operative pain	Drug: Oxycodone; exposure to opioids after Cesarean Section; Other Names: Opioid Exposure
NEONATE-INFANT cohort; 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; exposure to opioids after Cesarean Section; Other Names: Opioid Exposure

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CYP2D6 genotyping will be utilized to characterize CYP2D6 Poor Metabolizers (PMs) and Ultrarapid Metabolizers (UMS)-neonatal	A blood sample will be collected to assess polymorphisms of genotypes, epigenetics and gene expression affecting opioid effectiveness, metabolism and transport. CYP2D6 genotyping	Obtained during controlled delivery
CYP2D6 genotyping will be utilized to characterize CYP2D6 Poor Metabolizers (PMs) and Ultrarapid Metabolizers (UMS)-maternal	A blood sample will be collected to assess polymorphisms of genotypes, epigenetics and gene expression affecting opioid effectiveness, metabolism and transport. CYP2D6 genotyping	Obtained during controlled delivery
Opioid dependence (OD)	Clinical Opiate Withdrawal Scale (COWS). Minimum score: 0, Maximum score: 31. The higher the score, the more severe the withdrawal syndrome.	5-7 days after surgery and 3 to 12 months after surgery
Opioid Misuse Prediction	Opioid Risk Tool- score of 3 or less indicates low risk for future opioid use, 4-7 indicates moderate risk, score of 8 or higher indicates high risk	Before scheduled surgery and 1 week and 3 months post-op
Quality of Life after surgery	WHO Quality of Life Scale (0-100). Minimum score: 4, Maximum score: 20. Raw scores are converted to percentage values which is on a typical 0-100 scale.	1, 3, 6, 12 months post-op
Quality of Breastfeeding	LATCH Assessment Tool. The LATCH tool assigns a numerical score of 0, 1, or 2 to five key components of breastfeeding for a possible score of 10 points. Minimum score: 0, Maximum score: 10. Clinically a mom needs to have a score of 8 or higher to be discharged.	From time of surgery to time of discharge up to 30 days post-surgery
Screener and Opioid Assessment for Patients with Pain- Revised (SOAPP®-R)	Minimum score: 0, Maximum score: 96. A score of 18 or higher is considered positive.	1 week post-op and 1, 3, 6, 12 months post-op
Functional Recovery after surgery	Functional Disability Inventory (FDI). Minimum score: 0, Maximum score: 60. Higher scores indicate greater general functional limitations or increasing difficulty with the tasks and activities.	1 week and 3, 6, 12 months post-op
Pain Catastrophizing Scale	13 items scored from 0-4 with high score of 52, higher score indicates increased pain Catastrophizing	From day of surgery to 12 months post-op

Collaborators and Investigators

• Sponsor: Grace Lim, MD, MS
• Investigators: Principal Investigator: Grace Lim, MD MSc, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2022
• Primary Completion (Actual): September 24, 2023
• Study Completion (Actual): June 1, 2024

Study Registration Dates

• First Submitted: March 6, 2022
• First Submitted That Met QC Criteria: March 6, 2022
• First Posted (Actual): March 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 5, 2024
• Last Update Submitted That Met QC Criteria: July 3, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Personalized Care
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Oxycodone
• Other Study ID Numbers: STUDY21070164

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No