Personalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB) (PPAP Spine)

Senthil Sadhasivam

Status: Enrolling

Conditions: Spine Fusion; PPAP

Treatments: Diagnostic Test: Preoperative Genotyping

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05367609

STUDY21090075

TR003719 (Other Grant/Funding Number)

Details and patient eligibility

About

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 children undergoing painful surgery.

Full description

Aim 1. Develop and implement a perioperative precision analgesia platform (PPAP) by linking genomics to opioid metabolism, CPIC guidelines, precision dosing, clinical safety, and personalizing analgesia.

Aim 2. Implement and evaluate PPAP in children undergoing major inpatient surgery, posterior spinal fusion (PSF)

1. Determine genetic factors predisposing children to immediate and long-term postoperative methadone and oxycodone related adverse effects including RD, PONV, opioid dependence, and CPSP

   The PI postulate that specific CYP2B6, ABCB1, OPRM1, FAAH, and CYP2D6 variants identify children at risk for poor pain relief, RD, PONV, opioid dependence, and CPSP in the postoperative period.

2. Determine genetic variants-based perioperative dosing and outpatient prescribing of opioids

The PI hypothesize that CYP2B6 and CYP2D6 variants will explain pharmacokinetic variations of methadone and oxycodone, determine the right doses, and implement precision opioid use for optimal clinical outcomes

Enrollment: 300 estimated patients

Sex: All

Ages: 10 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Children ages 10 to 21
• ASA physical status 1 to 3
• Undergoing Posterior-Lateral Spinal Fusion
• Receives in-patient opioids
• Prescribed opioids at discharge

Exclusion criteria

• Serious illness
• Preoperative severe pain
• Preoperative opioid use or misuse

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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300 participants in 1 patient group

Children undergoing Spine Fusion Surgery

Other group

Description:

This arm will include approximately 300 children undergoing spine fusion surgery 1. Pharmacokinetic (PK): collection of 10-13 serial blood samples to determine serum levels of methadone/oxycodone and its metabolites 2. Pharmacogenetic (PG): Preoperative CYP2D6 genotyping (for preferential recruitment of CYP2D6 PMs and UMs). This will be collected in the pre-operative clinic via blood if there are clinical labs needed for standard of care. If no blood is needed in the pre-op clinic, the investigators will collect this via saliva. Postoperative Analgesia Dose and PK Sampling Schedule: Clinical care providers are blinded to CYP2D6/CYP2B6 when prescribing oxycodone/methadone; and genetic analysis of proposed targeted genes. Results of these samples will be used to determine personalized analgesia plan.

Treatment:

Diagnostic Test: Preoperative Genotyping