Precision Opioid Care After Cesarean Delivery (PRECISE-CD)

Opioid Use Clinical Trial

— PRECISE-CD  

Official title:

Avoiding Adverse Opioid Outcomes With Proactive Precision Care Following Cesarean Delivery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05280743
• Other study ID #: STUDY21070164
• Status: Active, not recruiting
• Start date: March 28, 2022
• Est. completion date: June 1, 2024

Study information

• Verified date: February 2024
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 341
• Est. completion date: June 1, 2024
• Est. primary completion date: September 24, 2023
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cesarean Section Complications
• Opioid Use

Intervention

Drug:
• Oxycodone
exposure to opioids after Cesarean Section

Locations

Country	Name	City	State
United States	Magee Women's Hospital of UPMC	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Grace Lim, MD, MS

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Total Maternal Inpatient Opioid Use	measured in milligrams of Morphine Equivalents	From time of surgery to discharge-- up to 3 days post-surgery
Secondary	Extended Hospital Length of Stay-Maternal	Yes/No Proportion of Women discharged beyond 72-hours post-surgery	From surgery to 72 hours postoperation
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	Neonatal Limpness (reporting limpness > 0, or not limp =0)	Proportion of Infants with Limpness reported	From birth to 72-hours post-delivery
Secondary	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)