Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section

Not Applicable

Recruiting

• Conditions: Cesarean Section Complications; Opioid Use
• Interventions: Diagnostic Test: Preoperative Genotyping

• Registration Number: NCT05380531
• Lead Sponsor: Senthil Sadhasivam

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-04-19
• Study First Submitted QC: 2022-05-12
• Study First Posted: 2022-05-19
• Study Start: 2022-12-05
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-03
• Last Update Posted: 2024-10-08
• Primary Completion: 2026-04-30
• Study Completion: 2026-10-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 600

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

1. Health conditions including uncontrolled diabetes (gestational or pre-existing) or hypertension (pre-eclampsia, eclampsia, or chronic)
2. Any history of opioid misuse before or during pregnancy-per self-report and clinical notes
3. Preoperative severe pain and opioid use/misuse, allergy to oxycodone
4. Allergy to oxycodone
5. Significant neurological disorders, liver and renal diseases

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Infant	Preoperative Genotyping	Infant subject will have genotyping blood draw performed only at the time of controlled delivery (CD)
Mother undergoing planned Cesarean section	Preoperative Genotyping	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.

Primary Outcome Measures

Name	Time	Method
Look at genetic factors predisposing patients to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)	At home up to 1 year post-surgery	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
Look at genetic factors predisposing patients to inadequate surgical pain relief with oxycodone	At home up to 1 year post-surgery	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.

Secondary Outcome Measures

Name	Time	Method
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.	Pre-operative to post-operative day 2	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.

Trial Locations

Locations (2)

UPMC Magee Women's Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States