Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section (PPAP C-Section)

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

Study Overview

• Status: Recruiting
• Conditions: Cesarean Section Complications; Opioid Use
• Intervention / Treatment: Diagnostic test: Preoperative Genotyping

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 Type: Interventional
• Enrollment (Estimated): 700
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Senthilkumar Sadhasivam, MD, MPH; Phone Number: 4126472994; Email: sadhasivams@upmc.edu
• Study Contact Backup: Name: Dayana Alsamsam, MPH; Email: alsamsamd@upmc.edu

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Riley Children's Hospital- Clinics / Labor and Delivery Unit
      • Principal Investigator: David M. Haas, MD
      • Contact: David M. Haas, MD; Phone Number: 317-880-3960; Email: dahaas@iu.edu
      • Contact: Jill Wallace, CIP; Phone Number: 317-278-2311; Email: jilawall@iu.edu
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University Hospital
      • Contact: Arvind Palanisamy, MD; Phone Number: 314-362-2330; Email: arvind.palanisamy@wustl.edu
      • Contact: Carissa Minder; Phone Number: 314-747-6845; Email: Carissa.minder@wustl.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15260
      • Recruiting
      • University of Pittsburgh
      • Contact: Amy Monroe, MPH; Phone Number: 412-623-6382; Email: monroeal@upmc.edu
    • Pittsburgh, Pennsylvania, United States, 15213
      • Not yet recruiting
      • UPMC Magee Women's Hospital
      • Contact: Katherine Grace Lim, MD; Phone Number: 412-641-4260; Email: limkg2@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mother undergoing planned Cesarean section; 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.	Diagnostic test: Preoperative Genotyping; Genotype based risk prediction and personalized pain management
Experimental: Infant; Infant subject will have genotyping blood draw performed only at the time of controlled delivery (CD)	Diagnostic test: Preoperative Genotyping; Genotype based risk prediction and personalized pain management

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Look at genetic factors predisposing patients to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)	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 immediate post-surgical period (4 days) in the hospital	Immediately post-surgery during hospital stay
Look at genetic factors predisposing patients to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)	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	At home up to 1 year post-surgery
Look at genetic factors predisposing patients to inadequate surgical pain relief with oxycodone	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 immediate post-surgical period (4 days) in the hospital. 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.	Immediately post-surgery during hospital stay
Look at genetic factors predisposing patients to inadequate surgical pain relief with oxycodone	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.	At home up to 1 year post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Pre-operative to post-operative day 2

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with chronic persistent surgical pain (CPSP) up to 1-year post-surgery	Patients will be asked to complete psychological questionnaires post-surgery to assess psycho-psychological factors that may correlate with CPSP. CPSP is defined as pain that develops after a surgical procedure and lasts at least 3 months and significantly affects health-related quality of life.	Post-operative up to 1-year
Look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with opioid dependence (OD) up to 1-year post-surgery	Patients will be asked to complete psychological questionnaires post-surgery to assess psycho-psychological factors that may correlate with opioid dependence (OD). OD will be determined using the validated Sophia Observation Withdrawal Symptoms Scale (SOS). The SOS is based on a 15-point scale.	Post-operative up to 1-year
Look at OPRM1 epigenetics and OPRM1, FAAH, GCH1, DRD2 variants to find correlations with opioid dependence (OD) up to 1-year post-surgery	Patients will be asked to complete psychological questionnaires post-surgery to assess psycho-psychological factors that may correlate with opioid dependence (OD). OD will be determined using the Clinical Opiate Withdrawal Scale (COWS). The COWS is based on a scale with a minimum score of 5 and maximum score of 48; 5-12 = mild, 13-24 = moderate, 25-36 = moderately severe, more than 36 = severe withdrawal	Post-operative up to 1-year

Collaborators and Investigators

• Sponsor: Senthil Sadhasivam
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Senthilkumar Sadhasivam, MD, MPH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: May 12, 2022
• First Posted (Actual): May 19, 2022

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 6, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Opioid Exposure
• Other Study ID Numbers: STUDY21100167; 1U01TR003719-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current IPD sharing plan anticipated

Drug and device information, study documents

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