A Study of Intrathecal Hydromorphone for Pediatric Idiopathic Scoliosis Repair

Identification of the Optimal Analgesic Dose of Intrathecal Hydromorphone for Pediatric Patients Undergoing Posterior Spine Surgery for Idiopathic Scoliosis

The purpose of this study is to identify a dose of intrathecal hydromorphone (opioid pain medicine) that optimizes pain control but minimizes side effects historically seen with this class of pain medications.

Study Overview

• Status: Terminated
• Conditions: Pain Control
• Intervention / Treatment: Drug: Hydromorphone 2.5 mcg/kg; Drug: Hydromorphone 2.75 mcg/kg; Drug: Hydromorphone 3 mcg/kg; Drug: Hydromorphone 3.25 mcg/kg; Drug: Hydromorphone 3.5 mcg/kg; Drug: Hydromorphone 4 mcg/kg; Drug: Hydromorphone 4.5 mcg/kg; Drug: Hydromorphone 5 mcg/kg; Drug: Hydromorphone 5.5 mcg/kg; Drug: Hydromorphone 6 mcg/kg; Drug: Hydromorphone 6.5 mcg/kg; Drug: Hydromorphone 7 mcg/kg

Detailed Description

This study is a sequential coin based up-down dose allocation method with the goal of identifying the ED90 for intrathecal hydromorphone (ITH) in idiopathic adolescent scoliosis repair via the posterior approach. A starting dose of 3.5 mcg/kg of hydromorphone was determined by current practice at the institution as well as upon review of available literature of previously used ITM doses in pediatric spine patients. Subsequent participants will receive higher (step "up") or lower (step "down") from this starting dose. Steps "down" from the starting dose will be smaller than steps "up" to ensure maintenance of adequate analgesia and to allow more accurate estimate of the optimal dose should it decrease beyond our starting dose. Steps "up" from the starting dose were chosen based on commonly used weight-based doses in our current practice. A maximum dose of 400 mcg, despite patient weight, was determined based on expert consensus and review preparatory to research query. Each patient was assigned to a weight-based dose arm, between 3.5mcg/kg-7.0mcg/kg or up to a maximum of 400 mcg. The anesthesiologist covering the case (high lumbar or thoracic corrections) or the surgeon (low lumbar corrections) will administer the medication at the low lumbar level.

ITH dose adjustments for subsequent study patients will be based on the efficacy of the dose used with the prior patient. Efficacious ITH administration will be defined as all NRS scores ≤5 within the first 18 hours after administration (binary outcome). If the NRS score was >5 within 18 hours or if the patient required supplemental opioid administration for pain control (suggestive of insufficient analgesia), the dose will be increased for the next enrolled study patient. If the pain score remains ≤5 within 18 hours of opioid administration, the next patient will receive the next lower dose or the same dose as the previous patient. Patients excluded after randomization will be removed from the study.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- Undergoing spinal surgery with a posterior approach for idiopathic scoliosis.

Exclusion criteria:

• Patients with pre-surgical elevated pain scores (≥ 3/10 on Numeric Rating Scale (NRS)), history of chronic pain, or pre-surgical opioid use will not be included.
• Patients with contraindications to spinal anesthesia (anatomical abnormality or elevated bleeding or infection risks) will not be included.
• Patients for whom the protocol is violated (inability to perform postoperative data collection), or the study/procedure was aborted will not be included in analysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intrathecal Hydromorphone 2.5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 2.5 mcg/kg; 2.5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 2.75 mcg/kg; Subjects undergoing posterior spinal surgery will receive 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 2.75 mcg/kg; 2.75 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 3 mcg/kg; Subjects undergoing posterior spinal surgery will receive 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 3 mcg/kg; 3 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 3.25 mcg/kg; Subjects undergoing posterior spinal surgery will receive 3.25 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 3.25 mcg/kg; 3.25 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 3.5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 3.5 mcg/kg; 3.5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 4 mcg/kg; Subjects undergoing posterior spinal surgery will receive 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 4 mcg/kg; 4 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 4.5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 4.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 4.5 mcg/kg; 4.5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 5 mcg/kg; 5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 5.5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 5.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 5.5 mcg/kg; 5.5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 6 mcg/kg; Subjects undergoing posterior spinal surgery will receive 6 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 6 mcg/kg; 6 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 6.5 mcg/kg; Subjects undergoing posterior spinal surgery will receive 6.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 6.5 mcg/kg; 6.5 mcg/kg intrathecal
Experimental: Intrathecal Hydromorphone 7 mcg/kg; Subjects undergoing posterior spinal surgery will receive 7 mcg/kg hydromorphone in the intrathecal space at the low lumbar level	Drug: Hydromorphone 7 mcg/kg; 7 mcg/kg intrathecal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity (Area Under the Curve Pain)	Pain intensity reported during the first 18 hours after intrathecal opioid administration. Reported by the patient using an 11-point numeric visual analogue scale (NRS) with 0=no pain and 10=worst pain ever. Subjects were asked to rate their pain approximately 9 different times within the first 18 hours after intrathecal hydromorphone administration. The sum of the patients' pain scores was calculated to determine pain intensity. Total scores ranging from 0 to 90 with higher scores indicating more severe pain. Pain scores over the first 18 hours were used to calculate the Area Under the Curve (AUC) using the trapezoidal rule.	18 hours after intrathecal hydromorphone administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Needing Dual Anti-pruritic Agents	The number of subjects who needed dual anti-pruritic agents (Nubain or naloxone (beyond the protocol infusion rate of 0.25 mcg/kg/min)).	24 postoperative hours
Maximum Pain Scores	Highest pain score reported during the first 18 hours after intrathecal opioid administration. Reported by the patient using an 11-point numeric visual analogue scale (NRS) with total scores ranging from 0=no pain and 10=worst pain ever with higher scores indicating more severe pain.	18 hours after intrathecal hydromorphone administration
Oral Morphine Equivalents Consumption	Total oral morphine equivalents (OME) consumption in the first 24 hours after intrathecal hydromorphone administration. Intrathecal hydromorphone will be included in total oral morphine equivalents consumption.	24 hours after intrathecal hydromorphone administration
Number of Subjects Needing Antiemetic Medications Postoperatively	The number of subjects who needed antiemetic medications to prevent or treat nausea and vomiting.	24 postoperative hours

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Kathryn Handlogten, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2023
• Primary Completion (Actual): October 27, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (Actual): September 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Posterior Spine Surgery; Pediatric Idiopathic Scoliosis Repair
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Perceptual Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Agnosia; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Hydromorphone
• Other Study ID Numbers: 22-006823

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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