Trial Outcomes & Findings for Intrathecal Opioids for Colorectal Resection (NCT NCT04752033)

NCT ID: NCT04752033

Last Updated: 2024-03-26

Results Overview

Failure was reported as a pain score of over 4/10 on a Numeric Rating Scale (NRS), scale range 0-10, 0 being no pain and 10 being the worst pain imaginable

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

80 participants

Primary outcome timeframe

12 hours after intrathecal (IT) drug administration

Results posted on

2024-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	Morphine 50 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Overall Study STARTED	2	5	4	4	4	1	4	16	6	10	6	2	1	3	12
Overall Study COMPLETED	2	5	4	4	4	1	4	16	6	10	6	2	1	3	12
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

race

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm	Total n=80 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants	0 Participants	0 Participants n=19 Participants	0 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	0 Participants n=3 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants	4 Participants n=7 Participants	3 Participants n=31 Participants	1 Participants n=30 Participants	3 Participants n=3 Participants	15 Participants n=6 Participants	4 Participants n=114 Participants	8 Participants	6 Participants n=19 Participants	0 Participants n=4 Participants	1 Participants n=7 Participants	3 Participants n=7 Participants	8 Participants n=3 Participants	66 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants	2 Participants n=114 Participants	2 Participants	0 Participants n=19 Participants	2 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	4 Participants n=3 Participants	14 Participants n=4 Participants
Age, Continuous	47 years n=99 Participants	40 years n=107 Participants	45 years n=206 Participants	47.5 years n=7 Participants	57.5 years n=31 Participants	39 years n=30 Participants	56 years n=3 Participants	54 years n=6 Participants	65.6 years n=114 Participants	53 years	51 years n=19 Participants	73 years n=4 Participants	33 years n=7 Participants	44 years n=7 Participants	62 years n=3 Participants	52 years n=4 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	5 Participants n=107 Participants	3 Participants n=206 Participants	2 Participants n=7 Participants	2 Participants n=31 Participants	0 Participants n=30 Participants	3 Participants n=3 Participants	8 Participants n=6 Participants	2 Participants n=114 Participants	4 Participants	3 Participants n=19 Participants	1 Participants n=4 Participants	0 Participants n=7 Participants	0 Participants n=7 Participants	8 Participants n=3 Participants	41 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants	2 Participants n=31 Participants	1 Participants n=30 Participants	1 Participants n=3 Participants	8 Participants n=6 Participants	4 Participants n=114 Participants	6 Participants	3 Participants n=19 Participants	1 Participants n=4 Participants	1 Participants n=7 Participants	3 Participants n=7 Participants	4 Participants n=3 Participants	39 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	0 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	0 Participants n=114 Participants • race	0 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	0 Participants n=3 Participants • race	0 Participants n=4 Participants • race
Race (NIH/OMB) Asian	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	0 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	0 Participants n=114 Participants • race	0 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	0 Participants n=3 Participants • race	0 Participants n=4 Participants • race
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	0 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	00 Participants n=114 Participants • race	0 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	0 Participants n=3 Participants • race	0 Participants n=4 Participants • race
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	0 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	0 Participants n=114 Participants • race	1 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	1 Participants n=3 Participants • race	2 Participants n=4 Participants • race
Race (NIH/OMB) White	2 Participants n=99 Participants • race	5 Participants n=107 Participants • race	4 Participants n=206 Participants • race	3 Participants n=7 Participants • race	4 Participants n=31 Participants • race	1 Participants n=30 Participants • race	4 Participants n=3 Participants • race	16 Participants n=6 Participants • race	6 Participants n=114 Participants • race	9 Participants race	6 Participants n=19 Participants • race	2 Participants n=4 Participants • race	1 Participants n=7 Participants • race	3 Participants n=7 Participants • race	11 Participants n=3 Participants • race	77 Participants n=4 Participants • race
Race (NIH/OMB) More than one race	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	0 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	0 Participants n=114 Participants • race	0 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	0 Participants n=3 Participants • race	0 Participants n=4 Participants • race
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants • race	0 Participants n=107 Participants • race	0 Participants n=206 Participants • race	1 Participants n=7 Participants • race	0 Participants n=31 Participants • race	0 Participants n=30 Participants • race	0 Participants n=3 Participants • race	0 Participants n=6 Participants • race	0 Participants n=114 Participants • race	0 Participants race	0 Participants n=19 Participants • race	0 Participants n=4 Participants • race	0 Participants n=7 Participants • race	0 Participants n=7 Participants • race	0 Participants n=3 Participants • race	1 Participants n=4 Participants • race
Region of Enrollment United States	2 participants n=99 Participants	5 participants n=107 Participants	4 participants n=206 Participants	4 participants n=7 Participants	4 participants n=31 Participants	1 participants n=30 Participants	4 participants n=3 Participants	16 participants n=6 Participants	6 participants n=114 Participants	10 participants	6 participants n=19 Participants	2 participants n=4 Participants	1 participants n=7 Participants	3 participants n=7 Participants	12 participants n=3 Participants	80 participants n=4 Participants
Body Mass Index	28.9 kg/m^2 n=99 Participants	26.9 kg/m^2 n=107 Participants	27.2 kg/m^2 n=206 Participants	35.1 kg/m^2 n=7 Participants	25.75 kg/m^2 n=31 Participants	27.81 kg/m^2 n=30 Participants	24.6 kg/m^2 n=3 Participants	30.55 kg/m^2 n=6 Participants	28.4 kg/m^2 n=114 Participants	28.5 kg/m^2	30 kg/m^2 n=19 Participants	28.95 kg/m^2 n=4 Participants	21.53 kg/m^2 n=7 Participants	29.8 kg/m^2 n=7 Participants	26.3 kg/m^2 n=3 Participants	28 kg/m^2 n=4 Participants

PRIMARY outcome

Timeframe: 12 hours after intrathecal (IT) drug administration

Failure was reported as a pain score of over 4/10 on a Numeric Rating Scale (NRS), scale range 0-10, 0 being no pain and 10 being the worst pain imaginable

Outcome measures

Outcome measures
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Postoperative Pain Control	4.5 score on a scale Interval 2.0 to 7.0	1.6 score on a scale Interval 1.0 to 4.0	1.75 score on a scale Interval 0.0 to 4.0	2.75 score on a scale Interval 1.0 to 6.0	3.75 score on a scale Interval 0.0 to 8.0	8 score on a scale	3.75 score on a scale Interval 2.0 to 5.0	3.31 score on a scale Interval 0.0 to 9.0	3 score on a scale Interval 0.0 to 7.0	3.2 score on a scale Interval 0.0 to 7.0	1.6 score on a scale Interval 0.0 to 3.0	2.5 score on a scale Interval 2.0 to 3.0	4 score on a scale	4.3 score on a scale Interval 3.0 to 5.0	2.5 score on a scale Interval 1.0 to 10.0

SECONDARY outcome

Timeframe: 24 hours after IT drug administration

Reported as Numeric Rating Scale (NRS), scale range 0-10, 0 being no pain and 10 being the worst pain imaginable.

Outcome measures

Outcome measures
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Postoperative Pain Control	3 units on a scale Interval 2.0 to 4.0	2.2 units on a scale Interval 0.0 to 4.0	2.25 units on a scale Interval 1.0 to 4.0	3 units on a scale Interval 0.0 to 6.0	4.25 units on a scale Interval 3.0 to 7.0	7 units on a scale	4.5 units on a scale Interval 2.0 to 7.0	3.37 units on a scale Interval 0.0 to 8.0	4.33 units on a scale Interval 2.0 to 8.0	3.72 units on a scale Interval 1.0 to 7.0	2.4 units on a scale Interval 1.0 to 4.0	3.5 units on a scale Interval 3.0 to 4.0	3 units on a scale	3.66 units on a scale Interval 1.0 to 7.0	4 units on a scale Interval 0.0 to 10.0

SECONDARY outcome

Timeframe: 12 and 24 hours after IT drug administration

Population: At 12 hours and 24 hours

Nausea and vomiting, pruritus, sedation, respiratory depression. The ordinal subjective scale of mild, moderate, and severe will be used.

Outcome measures

Outcome measures
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Mild at 12 hours	2 participants	1 participants	2 participants	1 participants	2 participants	0 participants	1 participants	5 participants	3 participants	3 participants	3 participants	0 participants	0 participants	2 participants	2 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Moderate at 12 hours	0 participants	3 participants	1 participants	1 participants	1 participants	0 participants	0 participants	7 participants	0 participants	2 participants	1 participants	0 participants	0 participants	1 participants	2 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Moderate at 24 hours	0 participants	1 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants	0 participants	0 participants	1 participants	1 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Mild at 24 hours	0 participants	2 participants	3 participants	1 participants	3 participants	0 participants	3 participants	5 participants	2 participants	4 participants	3 participants	0 participants	1 participants	0 participants	1 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Severe at 24 hours	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	3 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus None at 24 hours	2 participants	0 participants	1 participants	1 participants	1 participants	0 participants	0 participants	2 participants	3 participants	4 participants	0 participants	1 participants	0 participants	0 participants	3 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Severe at 12 hours	0 participants	1 participants	0 participants	0 participants	0 participants	1 participants	1 participants	4 participants	0 participants	1 participants	1 participants	0 participants	0 participants	0 participants	5 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Sedation at 12 hours	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Respiratory Depression at 12 hours	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting None at 24 hours	2 participants	1 participants	3 participants	3 participants	2 participants	1 participants	1 participants	10 participants	6 participants	8 participants	2 participants	2 participants	1 participants	1 participants	7 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Mild at 24 hours	0 participants	2 participants	0 participants	1 participants	2 participants	0 participants	3 participants	3 participants	0 participants	2 participants	2 participants	0 participants	0 participants	1 participants	4 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting None at 12 hours	1 participants	2 participants	1 participants	3 participants	0 participants	1 participants	1 participants	7 participants	4 participants	5 participants	2 participants	0 participants	0 participants	1 participants	6 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Mild at 12 hours	0 participants	1 participants	2 participants	0 participants	1 participants	0 participants	0 participants	3 participants	2 participants	3 participants	2 participants	1 participants	0 participants	0 participants	3 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Moderate at 12 hours	1 participants	1 participants	1 participants	1 participants	2 participants	0 participants	2 participants	3 participants	0 participants	2 participants	1 participants	1 participants	1 participants	2 participants	1 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Nausea and Vomiting Severe at 12 hours	0 participants	1 participants	0 participants	0 participants	1 participants	0 participants	1 participants	3 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	2 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus None at 12 hours	0 participants	0 participants	1 participants	2 participants	1 participants	0 participants	2 participants	0 participants	3 participants	4 participants	1 participants	2 participants	1 participants	0 participants	3 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Moderate at 24 hours	0 participants	1 participants	0 participants	2 participants	0 participants	1 participants	0 participants	6 participants	0 participants	1 participants	3 participants	0 participants	0 participants	3 participants	2 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Pruritus Severe at 24 hours	0 participants	2 participants	0 participants	0 participants	0 participants	0 participants	1 participants	3 participants	1 participants	1 participants	0 participants	1 participants	0 participants	0 participants	6 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Sedation at 24 hours	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Presence and Severity of Opioid-related Side Effects at Their Highest Doses Respiratory Depression at 24 hours	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 12 and 24 hours after highest IT drug administration

OBAS is a validated measure incorporating both effectiveness of pain control and unwanted effects related to analgesic treatment. The scale ranges from 0 to 24, with higher the score, worse the pain control.

Outcome measures

Outcome measures
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Overall Benefits of Analgesia Score (OBAS) At 12 hours	5.5 score on a scale Interval 2.0 to 9.0	4.8 score on a scale Interval 3.0 to 6.0	2.33 score on a scale Interval 1.0 to 4.0	3.5 score on a scale Interval 1.0 to 7.0	4.5 score on a scale Interval 2.0 to 6.0	3 score on a scale	3.33 score on a scale Interval 1.0 to 6.0	5.625 score on a scale Interval 0.0 to 16.0	2.8 score on a scale Interval 0.0 to 8.0	4.09 score on a scale Interval 2.0 to 7.0	3 score on a scale Interval 0.0 to 5.0	2.5 score on a scale Interval 1.0 to 4.0	7 score on a scale	5.5 score on a scale Interval 3.0 to 8.0	4.5 score on a scale Interval 0.0 to 15.0
Overall Benefits of Analgesia Score (OBAS) At 24 hours	3.5 score on a scale Interval 0.0 to 7.0	3.2 score on a scale Interval 2.0 to 5.0	2.5 score on a scale Interval 1.0 to 4.0	2.75 score on a scale Interval 2.0 to 4.0	4 score on a scale Interval 0.0 to 10.0	1 score on a scale	3.75 score on a scale Interval 1.0 to 8.0	5.13 score on a scale Interval 0.0 to 16.0	3.6 score on a scale Interval 0.0 to 9.0	3.27 score on a scale Interval 0.0 to 7.0	3.8 score on a scale Interval 1.0 to 6.0	2.5 score on a scale Interval 2.0 to 3.0	10 score on a scale	4 score on a scale Interval 0.0 to 8.0	4.08 score on a scale Interval 0.0 to 18.0

SECONDARY outcome

Timeframe: 24 hours after IT drug administration

QoR 15 score is a multidimensional, valid, reliable, responsive, and easy-to-use method of measuring quality in patients' postoperative recovery. The scale ranges from 0 to 150, with higher the score, the better the recovery is.

Outcome measures

Outcome measures
Measure	Morphine 50 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 Participants Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Quality of Recovery (QoR) 15 Score	114.5 score on a scale Interval 98.0 to 130.5	120.5 score on a scale Interval 105.0 to 133.5	108.5 score on a scale Interval 90.0 to 133.0	123.75 score on a scale Interval 118.0 to 139.0	106.25 score on a scale Interval 75.0 to 139.0	131 score on a scale	116.75 score on a scale Interval 97.0 to 140.0	115.9 score on a scale Interval 70.0 to 142.0	119 score on a scale Interval 97.0 to 149.0	119.5 score on a scale Interval 83.0 to 135.0	117.8 score on a scale Interval 105.0 to 141.0	126 score on a scale Interval 120.0 to 132.0	104 score on a scale	102 score on a scale Interval 85.0 to 125.0	116.75 score on a scale Interval 39.0 to 147.0

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Morphine 50 mcg n=2 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 100 mcg n=5 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 150 mcg n=4 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 200 mcg n=4 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 250 mcg n=4 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 300 mcg n=1 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 350 mcg n=4 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Morphine 400 mcg n=16 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the hydromorphone arm Morphine: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a morphine dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 50 mcg n=6 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 75 mcg n=10 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 100 mcg n=6 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 125 mcg n=2 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 150 mcg n=1 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 175 mcg n=3 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.	Hydromorphone 200 mcg n=12 participants at risk Subjected to sequential up and down dose titration using biased coin method in parallel with the morphine arm Hydromorphone: Dose titration utilizing will be done using sequential up and down design using biased coin method. All participant will receive a hydromorphone dose that is within the range of doses currently utilized clinically and no participant will receive placebo only.
Gastrointestinal disorders Nausea and Vomiting	0.00% 0/2 • 12 and 24 hours	20.0% 1/5 • Number of events 1 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/1 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	18.8% 3/16 • Number of events 3 • 12 and 24 hours	0.00% 0/6 • 12 and 24 hours	0.00% 0/10 • 12 and 24 hours	0.00% 0/6 • 12 and 24 hours	0.00% 0/2 • 12 and 24 hours	0.00% 0/1 • 12 and 24 hours	0.00% 0/3 • 12 and 24 hours	0.00% 0/12 • 12 and 24 hours
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/2 • 12 and 24 hours	40.0% 2/5 • Number of events 2 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/4 • 12 and 24 hours	0.00% 0/1 • 12 and 24 hours	25.0% 1/4 • Number of events 1 • 12 and 24 hours	18.8% 3/16 • Number of events 3 • 12 and 24 hours	16.7% 1/6 • Number of events 1 • 12 and 24 hours	10.0% 1/10 • Number of events 1 • 12 and 24 hours	0.00% 0/6 • 12 and 24 hours	50.0% 1/2 • Number of events 1 • 12 and 24 hours	0.00% 0/1 • 12 and 24 hours	0.00% 0/3 • 12 and 24 hours	50.0% 6/12 • Number of events 6 • 12 and 24 hours

Additional Information

Dr. Joseph Pleticha

Mayo Clinic

Phone: 5073588378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place