NCT06626503

Evaluation of Analgesia for Spine Fusion Elective Surgery in Children

Prospective Randomized Evaluation of Analgesia for Spine Fusion Elective Surgery in Children (PRECISE Spine Trial)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 500 (estimated)
• Sponsor: Senthil Sadhasivam · Academic / Other
• Sex: All
• Age: 10 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

The multicenter PRECISE Analgesia (Prospective Randomized Evaluation of Analgesia for Idiopathic Scoliosis Spine Fusion Elective Surgery in Children) trials will a) implement and investigate the efficacy and safety of multidose methadone-based standardized enhanced recovery after surgery (ERAS) protocol, and b) develop personalized ERAS protocols including precision methadone and oxycodone dosing1,2 and c) personalized analgesia for the safe and effective opioid-sparing management of surgical pain after posterior spine fusion (PSF) in children.

Detailed description

Specific Aims Aim 1. Conduct a randomized clinical trial in posterior spine fusion (PSF) to compare acute pain relief, opioid-sparing efficacy, and safety of standardized perioperative multidose methadone-based enhanced recovery after surgery (ERAS) vs. standard-of-care non-methadone-based analgesia. Aim 2. Develop precision methadone dosing based on age, CYP2B6 and ORM1 variants, and alpha acid glycoprotein (AAG). Aim 3. Identify patient profiles that predict benefits from the assigned analgesia protocol to optimize clinical outcomes. Personalized risk prediction models will be developed and validated including genetic variants (i.e., CYP2B6, CYP2D6, ABCB1, OPRM1, and FAAH), and psychological and clinical factors to predict benefit with the assigned treatments (methadone or non-methadone) for pre-specified clinical endpoints (i.e., lower acute surgical pain, respiratory depression \[RD\], postoperative nausea and vomiting \[PONV\], opioid dependence \[OD\], and chronic postsurgical pain \[CPSP\]) in PSF. Overall Impact The investigators will develop actionable evidence for the efficacy of standardized, multidose, methadone-based ERAS protocols and will harness genetic, clinical, and psychological factors contributing to variability in methadone and oxycodone PK, acute surgical pain, transition to CPSP, opioid-induced PONV, RD, and dependence to develop personalized analgesia strategy and dosing for children undergoing PSF. Implementation of evidence-based standardized methadone-based ERAS pain management and individualized risk prediction will maximize acute surgical pain relief while minimizing opioid use and adverse events (AEs) in millions of children. Hypothesis The central hypothesis is that a standardized, multidose, methadone-based ERAS protocol will reduce acute surgical pain, overall opioid use, RD, PONV and CPSP compared with standard-of-care short-acting opioid-based analgesia in children undergoing PSF. The long-term goal is to proactively improve the safety and efficacy of surgical pain control while reducing opioid AEs and the opioid epidemic burden in all children undergoing inpatient surgeries. Further, we hypothesize that age, CYP2B6 and ORM1 variants, and AAG levels will explain methadone's PK variability and dose adjustments that correlate with optimal clinical outcomes, and that patient profiles based on genetic, psychological, and that clinical factors will predict benefits from the assigned analgesia protocol to optimize clinical outcomes.

Conditions

• Idiopathic Scoliosis

Interventions

Type	Name	Description
DRUG	Methadone based ERAS	Methadone intervention includes intraoperative intravenous methadone (1st dose: 0.1 mg/kg up to a maximum of 5 mg before incision; 2nd dose: 0.05 mg/kg up to a maximum of 2.5 mg 4 hours after 1st dose) and postoperatively, up to 4 oral doses of methadone every 12 hours before discharge as part of standardized multimodal analgesia in the hospital setting.
DRUG	Non-methadone based group	Non-methadone intervention includes standard opioid analgesia protocol without intra- and post-operative methadone per the current site standards. Postoperative pain medication is recommended when reported pain level is considered moderate or higher (≥4 on NRS and FLACC).

Timeline

• Start date: 2025-10-30
• Primary completion: 2029-01-31
• Completion: 2029-08-31
• First posted: 2024-10-04
• Last updated: 2026-02-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study