Personalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 7
- 主要终点
- Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)
研究概览
简要总结
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.
详细描述
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)
- 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
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children ages 10 to 21
- •ASA physical status 1 to 3
- •Undergoing Posterior-Lateral Spinal Fusion
- •Receives in-patient opioids
- •Prescribed opioids at discharge
排除标准
- •Serious illness
- •Preoperative severe pain
- •Preoperative opioid use or misuse
研究组 & 干预措施
Children undergoing Spine Fusion Surgery
This arm will include approximately 300 children undergoing spine fusion surgery
- Pharmacokinetic (PK): collection of 10-13 serial blood samples to determine serum levels of methadone/oxycodone and its metabolites
- 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.
干预措施: Preoperative Genotyping (Diagnostic Test)
结局指标
主要结局
Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)
时间窗: Immediately post-surgery
The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD and PONV in the immediate post-surgical period (4 days) in the hospital
Look at genetic factors predisposing children to postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV) at genetic factors predisposing children to inadequate surgical pain relief with oxycodone
时间窗: 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 children who experience RD and PONV in the post-surgical period at home up to 1-year
Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone
时间窗: 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 children who experience poor pain relief in the post-surgical period at home up to 1-year. Poor pain relief will be determined 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.
Look at genetic factors predisposing children to immediate postoperative opioid-adverse effects Respiratory Depression (RD) and Postoperative Nausea and Vomiting (PONV)
时间窗: Immediately post-surgery up to 4 days in patient
The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience RD and PONV in the immediate post-surgical period (4 days) in the hospital
Look at genetic factors predisposing children to inadequate surgical pain relief with oxycodone
时间窗: Immediately post-surgery
The investigators will look at specific CYP2D6, ABCB1, FAAH, OPRM1, and COMT variants to find correlations with children who experience poor pain relief in the immediate post-surgical period (4 days) in the hospital. Poor pain relief will be determined 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.
次要结局
- Look at the impact of CYP2D6 variants on oxycodone's clinical dosing in children to see if specific variants correlate with a need for lower or higher doses of analgesic(Pre-operative to post-operative day 2)
研究者
Senthil Sadhasivam
Professor
University of Pittsburgh