Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section

Opioid Use Clinical Trial

— PPAP C-Section  

Official title:

Personalized Perioperative Analgesia Platform (PPAP) for Cesarean Section

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05380531
• Other study ID #: STUDY21100167
• Secondary ID: 1U01TR003719-01A
• Status: Recruiting
• Phase: N/A
• Start date: December 5, 2022
• Est. completion date: October 30, 2026

Study information

• Verified date: November 2023
• Source: University of Pittsburgh
• Contact: Senthilkumar Sadhasivam, MD, MPH
• Phone: 4126472994
• Email: sadhasivams[@]upmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: October 30, 2026
• Est. primary completion date: April 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cesarean Section Complications
• Opioid Use

Intervention

Diagnostic Test:
• Preoperative Genotyping
Genotype based risk prediction and personalized pain management

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Senthil Sadhasivam	National Center for Advancing Translational Sciences (NCATS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	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	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