Trial Outcomes & Findings for A Study of Intrathecal Hydromorphone for Pediatric Idiopathic Scoliosis Repair (NCT NCT05552443)

Last Updated: 2026-05-14

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

31 participants

Primary outcome timeframe

18 hours after intrathecal hydromorphone administration

Results posted on

2026-05-14

Participant Flow

There were 31 subjects consented to the study, one of which was withdrawn from the study before study group assignment occurred.

0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.

Participant milestones

Participant milestones
Measure	Intrathecal Hydromorphone 3.5 mcg/kg Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.5 mcg/kg: 3.5 mcg/kg intrathecal	Intrathecal Hydromorphone 4 mcg/kg Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4 mcg/kg: 4 mcg/kg intrathecal	Intrathecal Hydromorphone 4.5 mcg/kg Subjects undergoing posterior spinal surgery received 4.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4.5 mcg/kg: 4.5 mcg/kg intrathecal	Intrathecal Hydromorphone 5 mcg/kg Subjects undergoing posterior spinal surgery received 5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5 mcg/kg: 5 mcg/kg intrathecal	Intrathecal Hydromorphone 5.5 mcg/kg Subjects undergoing posterior spinal surgery received 5.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5.5 mcg/kg: 5.5 mcg/kg intrathecal	Intrathecal Hydromorphone 6 mcg/kg Subjects undergoing posterior spinal surgery received 6 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6 mcg/kg: 6 mcg/kg intrathecal	Intrathecal Hydromorphone 6.5 mcg/kg Subjects undergoing posterior spinal surgery received 6.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6.5 mcg/kg: 6.5 mcg/kg intrathecal	Intrathecal Hydromorphone 7 mcg/kg Subjects undergoing posterior spinal surgery received 7 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 7 mcg/kg: 7 mcg/kg intrathecal
Overall Study STARTED	2	1	1	3	4	5	6	8
Overall Study COMPLETED	2	1	1	3	4	3	6	7
Overall Study NOT COMPLETED	0	0	0	0	0	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3 mcg/kg: 3 mcg/kg intrathecal	Intrathecal Hydromorphone 3.25 mcg/kg Subjects undergoing posterior spinal surgery received 3.25 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.25 mcg/kg: 3.25 mcg/kg intrathecal	Intrathecal Hydromorphone 3.5 mcg/kg Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.5 mcg/kg: 3.5 mcg/kg intrathecal	Intrathecal Hydromorphone 4 mcg/kg Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4 mcg/kg: 4 mcg/kg intrathecal	Intrathecal Hydromorphone 4.5 mcg/kg Subjects undergoing posterior spinal surgery received 4.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4.5 mcg/kg: 4.5 mcg/kg intrathecal	Intrathecal Hydromorphone 5 mcg/kg Subjects undergoing posterior spinal surgery received 5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5 mcg/kg: 5 mcg/kg intrathecal	Intrathecal Hydromorphone 5.5 mcg/kg Subjects undergoing posterior spinal surgery received 5.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5.5 mcg/kg: 5.5 mcg/kg intrathecal	Intrathecal Hydromorphone 6 mcg/kg Subjects undergoing posterior spinal surgery received 6 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6 mcg/kg: 6 mcg/kg intrathecal	Intrathecal Hydromorphone 6.5 mcg/kg Subjects undergoing posterior spinal surgery received 6.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6.5 mcg/kg: 6.5 mcg/kg intrathecal	Intrathecal Hydromorphone 7 mcg/kg Subjects undergoing posterior spinal surgery received 7 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 7 mcg/kg: 7 mcg/kg intrathecal	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.5 mcg/kg: 2.5 mcg/kg intrathecal	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.75 mcg/kg: 2.75 mcg/kg intrathecal
Overall Study Physician Decision	0	0	0	0	0	0	0	2	0	1	0	0

Baseline Characteristics

A Study of Intrathecal Hydromorphone for Pediatric Idiopathic Scoliosis Repair

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.5 mcg/kg: 2.5 mcg/kg intrathecal	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.75 mcg/kg: 2.75 mcg/kg intrathecal	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3 mcg/kg: 3 mcg/kg intrathecal	Intrathecal Hydromorphone 3.25 mcg/kg Subjects undergoing posterior spinal surgery received 3.25 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.25 mcg/kg: 3.25 mcg/kg intrathecal	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.5 mcg/kg: 3.5 mcg/kg intrathecal	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4 mcg/kg: 4 mcg/kg intrathecal	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4.5 mcg/kg: 4.5 mcg/kg intrathecal	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5 mcg/kg: 5 mcg/kg intrathecal	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 5.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5.5 mcg/kg: 5.5 mcg/kg intrathecal	Intrathecal Hydromorphone 6 mcg/kg n=5 Participants Subjects undergoing posterior spinal surgery received 6 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6 mcg/kg:6 mcg/kg intrathecal	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 6.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6.5 mcg/kg:6.5 mcg/kg intrathecal	Intrathecal Hydromorphone 7 mcg/kg n=8 Participants Subjects undergoing posterior spinal surgery received 7mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 7 mcg/kg:7 mcg/kg intrathecal	Total n=30 Participants Total of all reporting groups
Age, Categorical <=18 years	—	—	—	—	2 Participants n=97 Participants	1 Participants n=488 Participants	1 Participants n=825 Participants	3 Participants n=2 Participants	4 Participants n=3 Participants	5 Participants n=3 Participants	6 Participants n=3 Participants	8 Participants n=26 Participants	30 Participants n=128 Participants
Age, Categorical Between 18 and 65 years	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Age, Categorical >=65 years	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Sex: Female, Male Female	—	—	—	—	2 Participants n=97 Participants	0 Participants n=488 Participants	1 Participants n=825 Participants	3 Participants n=2 Participants	2 Participants n=3 Participants	3 Participants n=3 Participants	6 Participants n=3 Participants	4 Participants n=26 Participants	21 Participants n=128 Participants
Sex: Female, Male Male	—	—	—	—	0 Participants n=97 Participants	1 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	2 Participants n=3 Participants	2 Participants n=3 Participants	0 Participants n=3 Participants	4 Participants n=26 Participants	9 Participants n=128 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	1 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	1 Participants n=128 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	—	—	—	—	2 Participants n=97 Participants	1 Participants n=488 Participants	1 Participants n=825 Participants	3 Participants n=2 Participants	4 Participants n=3 Participants	4 Participants n=3 Participants	6 Participants n=3 Participants	8 Participants n=26 Participants	29 Participants n=128 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Race (NIH/OMB) White	—	—	—	—	2 Participants n=97 Participants	1 Participants n=488 Participants	1 Participants n=825 Participants	3 Participants n=2 Participants	2 Participants n=3 Participants	5 Participants n=3 Participants	4 Participants n=3 Participants	8 Participants n=26 Participants	26 Participants n=128 Participants
Race (NIH/OMB) American Indian or Alaska Native	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Race (NIH/OMB) Asian	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Race (NIH/OMB) Black or African American	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	2 Participants n=3 Participants	0 Participants n=3 Participants	2 Participants n=3 Participants	0 Participants n=26 Participants	4 Participants n=128 Participants
Race (NIH/OMB) More than one race	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Race (NIH/OMB) Unknown or Not Reported	—	—	—	—	0 Participants n=97 Participants	0 Participants n=488 Participants	0 Participants n=825 Participants	0 Participants n=2 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=26 Participants	0 Participants n=128 Participants
Region of Enrollment United States	—	—	—	—	2 participants n=97 Participants	1 participants n=488 Participants	1 participants n=825 Participants	3 participants n=2 Participants	4 participants n=3 Participants	5 participants n=3 Participants	5 participants n=3 Participants	8 participants n=26 Participants	29 participants n=128 Participants
Region of Enrollment Canada	—	—	—	—	0 participants n=97 Participants	0 participants n=488 Participants	0 participants n=825 Participants	0 participants n=2 Participants	0 participants n=3 Participants	0 participants n=3 Participants	1 participants n=3 Participants	0 participants n=26 Participants	1 participants n=128 Participants

PRIMARY outcome

Timeframe: 18 hours after intrathecal hydromorphone administration

Population: 0 in 2.5-3.0 mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design.

Outcome measures

Outcome measures
Measure	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 7 mcg/kg n=7 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.
Pain Intensity (Area Under the Curve Pain)	18.0 pain score units*hours Interval 18.0 to 18.0	17.2 pain score units*hours Interval 9.2 to 38.8	4.1 pain score units*hours Interval 0.0 to 36.6	50.0 pain score units*hours Interval 25.2 to 54.8	37.6 pain score units*hours Interval 19.3 to 86.2	27.5 pain score units*hours Interval 13.4 to 45.5	—	—	—	22.9 pain score units*hours Interval 20.7 to 25.1	17.8 pain score units*hours Interval 17.8 to 17.8

SECONDARY outcome

Timeframe: 24 postoperative hours

The number of subjects who needed dual anti-pruritic agents (Nubain or naloxone (beyond the protocol infusion rate of 0.25 mcg/kg/min)).

Outcome measures

Outcome measures
Measure	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 7 mcg/kg n=7 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.
Number of Subjects Needing Dual Anti-pruritic Agents	0 Participants	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	—	—	—	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 18 hours after intrathecal hydromorphone administration

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.

Outcome measures

Outcome measures
Measure	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 7 mcg/kg n=7 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.
Maximum Pain Scores	7.0 score on a scale Interval 7.0 to 7.0	3.0 score on a scale Interval 3.0 to 7.0	4.5 score on a scale Interval 0.0 to 5.0	4.0 score on a scale Interval 3.0 to 5.0	6.5 score on a scale Interval 4.0 to 8.0	5.0 score on a scale Interval 1.0 to 8.0	—	—	—	5.5 score on a scale Interval 4.0 to 7.0	6.0 score on a scale Interval 6.0 to 6.0

SECONDARY outcome

Timeframe: 24 hours after intrathecal hydromorphone administration

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.

Outcome measures

Outcome measures
Measure	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 7 mcg/kg n=7 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.
Oral Morphine Equivalents Consumption	143 mg Interval 143.0 to 143.0	193 mg Interval 153.0 to 258.0	191 mg Interval 171.0 to 240.0	232 mg Interval 222.0 to 237.0	240 mg Interval 197.0 to 285.0	228 mg Interval 174.0 to 263.0	—	—	—	131 mg Interval 126.0 to 135.0	163 mg Interval 163.0 to 163.0

SECONDARY outcome

Timeframe: 24 postoperative hours

The number of subjects who needed antiemetic medications to prevent or treat nausea and vomiting.

Outcome measures

Outcome measures
Measure	Intrathecal Hydromorphone 4.5 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 5.5 mcg/kg n=4 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6 mcg/kg n=3 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 6.5 mcg/kg n=6 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 7 mcg/kg n=7 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 3.5 mcg/kg n=2 Participants Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.	Intrathecal Hydromorphone 4 mcg/kg n=1 Participants Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level.
Number of Subjects Needing Antiemetic Medications Postoperatively	1 Participants	2 Participants	4 Participants	1 Participants	4 Participants	5 Participants	—	—	—	1 Participants	1 Participants

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intrathecal Hydromorphone 2.5 mcg/kg Subjects undergoing posterior spinal surgery received 2.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.5 mcg/kg: 2.5 mcg/kg intrathecal	Intrathecal Hydromorphone 2.75 mcg/kg Subjects undergoing posterior spinal surgery received 2.75 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 2.75 mcg/kg: 2.75 mcg/kg intrathecal	Intrathecal Hydromorphone 3 mcg/kg Subjects undergoing posterior spinal surgery received 3 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3 mcg/kg: 3 mcg/kg intrathecal	Intrathecal Hydromorphone 3.25 mcg/kg Subjects undergoing posterior spinal surgery received 3.25 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.25 mcg/kg: 3.25 mcg/kg intrathecal	Intrathecal Hydromorphone 3.5 mcg/kg n=2 participants at risk Subjects undergoing posterior spinal surgery received 3.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 3.5 mcg/kg: 3.5 mcg/kg intrathecal	Intrathecal Hydromorphone 4 mcg/kg n=1 participants at risk Subjects undergoing posterior spinal surgery received 4 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4 mcg/kg: 4 mcg/kg intrathecal	Intrathecal Hydromorphone 4.5 mcg/kg n=1 participants at risk Subjects undergoing posterior spinal surgery received 4.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 4.5 mcg/kg: 4.5 mcg/kg intrathecal	Intrathecal Hydromorphone 5 mcg/kg n=3 participants at risk Subjects undergoing posterior spinal surgery received 5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5 mcg/kg: 5 mcg/kg intrathecal	Intrathecal Hydromorphone 5.5 mcg/kg n=4 participants at risk Subjects undergoing posterior spinal surgery received 5.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 5.5 mcg/kg: 5.5 mcg/kg intrathecal	Intrathecal Hydromorphone 6 mcg/kg n=5 participants at risk Subjects undergoing posterior spinal surgery received 6 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6 mcg/kg: 6 mcg/kg intrathecal	Intrathecal Hydromorphone 6.5 mcg/kg n=6 participants at risk Subjects undergoing posterior spinal surgery received 6.5 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 6.5 mcg/kg: 6.5 mcg/kg intrathecal	Intrathecal Hydromorphone 7 mcg/kg n=8 participants at risk Subjects undergoing posterior spinal surgery received 7 mcg/kg hydromorphone in the intrathecal space at the low lumbar level Hydromorphone 7 mcg/kg: 7 mcg/kg intrathecal
Injury, poisoning and procedural complications Airway Trauma	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/2 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	100.0% 1/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/3 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/4 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/5 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/6 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/8 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.
Injury, poisoning and procedural complications Desaturations	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/2 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/3 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/4 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	20.0% 1/5 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/6 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	12.5% 1/8 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.
Injury, poisoning and procedural complications Apneas	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/2 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/3 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/4 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/5 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/6 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	12.5% 1/8 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.
Gastrointestinal disorders Nausea/Vomiting	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/2 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/3 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/4 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/5 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/6 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	12.5% 1/8 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.
Injury, poisoning and procedural complications Prolonged Sedation due to Inability to Meet Extubation Criteria	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	— 0/0 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/2 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/1 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/3 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	25.0% 1/4 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/5 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/6 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.	0.00% 0/8 • Adverse events were collected from the time of informed consent through study completion, approximately 24 hours. 0 in 2.5-3.25mcg/kg arms as SDMS didn't assign subjects to those doses due to ITH dose for 1st subject being 3.5mcg/kg and subsequent subjects dose assignmts following a biased-coin up-down sequential allocation design. Adjustments made in 0.5mcg/kg increments based on efficacy defined asNRS≤5 within18hrs post-ITH. If subject had NRS\>5,the next subject received next higher dose.If subject had NRS≤5,next subject had0.89 chance of receiving same dose and0.11 chance of receiving next lower dose.

Additional Information

Kathryn Handlogten, M.D.

Mayo Clinic

Phone: 507-255-4236

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place