Clinical trial NCT05280743: Precision Opioid Care After Cesarean Delivery (PRECISE-CD)
Official title: Avoiding Adverse Opioid Outcomes With Proactive Precision Care Following Cesarean Delivery
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cesarean Section Complications
Opioid Use
Keywords: Personalized Care
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2022-03-15
Enrollment: 341
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants who have Cesarean Delivery and who plan to breast feed their infants

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Opioid-Induced Adverse Effects-PROPORTION of maternal participants with RD
timeFrame: From time of surgery to time of discharge up to 3 days post-surgery
measure: Opioid-Induced Adverse Effects-PROPORTION of maternal participants with PONV
timeFrame: From time of surgery to time of discharge up to 3 days post-surgery
Secondary outcomes:
measure: Maternal Post-operative Pain Scores
timeFrame: From time of delivery to 12-month post-surgery
measure: Total Maternal Inpatient Opioid Use
timeFrame: From time of surgery to discharge-- up to 3 days post-surgery
measure: Extended Hospital Length of Stay-Maternal
timeFrame: From surgery to 72 hours postoperation
measure: Length of prescribed opioid use (For Mothers; in days)
timeFrame: From day of surgery to 12-month post-surgery
measure: Neonatal Sedation-- PROPORTION of infants with Sedation
timeFrame: From birth to 7-days post-birth
measure: Neonatal Respiratory Depression--PROPORTION of neonates diagnosed with RD
timeFrame: From birth to time of discharge (up to 3 days post-birth)
measure: Extended Hospital Length of Stay-Neonate
timeFrame: From time of delivery to 72-hours post-delivery
measure: Neonatal Limpness (reporting limpness > 0, or not limp =0)
timeFrame: From birth to 72-hours post-delivery
measure: Proportion of Neonates Exhibiting opioid withdrawal
timeFrame: Birth to 3-days postpartum (or discharge from hospital)
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Magee Women's Hospital of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Grace Lim, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: