Trial Outcomes & Findings for Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery (NCT NCT03011307)
NCT ID: NCT03011307
Last Updated: 2022-11-23
Results Overview
Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
TERMINATED
PHASE2
126 participants
The first day after hospital discharge
2022-11-23
Participant Flow
Enrollment occurred from January 12, 2017 to August 3, 2020 at the Orthopeadic Clinics of Atrium Wake Forest Baptist and Davie County facilities.
Enrollment occurred greater or equal to 2 weeks prior to surgery. A total of 28 individuals were excluded prior to assignment to groups during the period prior to surgery because of withdrawal of consent (n=25) or cancellation of the planned surgery (n=3).
Participant milestones
| Measure |
Oxytocin
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
48
|
|
Overall Study
COMPLETED
|
44
|
46
|
|
Overall Study
NOT COMPLETED
|
6
|
2
|
Reasons for withdrawal
| Measure |
Oxytocin
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Overall Study
Did not receive study drug: blood pressure or heart rate instability before spinal injection
|
3
|
2
|
|
Overall Study
Did not receive study drug: unable to place spinal needle
|
2
|
0
|
|
Overall Study
Did not receive study drug: unable to obtain study drug from formulating pharmacy
|
1
|
0
|
Baseline Characteristics
Efficacy of Intrathecal Oxytocin to Speed Recovery After Hip Surgery
Baseline characteristics by cohort
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
24 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
20 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
59 years
STANDARD_DEVIATION 10 • n=7 Participants
|
61 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
90 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
44 participants
n=5 Participants
|
46 participants
n=7 Participants
|
90 participants
n=5 Participants
|
|
Worst daily pain
|
5.0 units on a scale
STANDARD_DEVIATION 2.9 • n=5 Participants
|
5.8 units on a scale
STANDARD_DEVIATION 2.3 • n=7 Participants
|
5.4 units on a scale
STANDARD_DEVIATION 2.7 • n=5 Participants
|
|
Daily steps
|
6440 Steps per day
STANDARD_DEVIATION 4120 • n=5 Participants
|
6918 Steps per day
STANDARD_DEVIATION 4613 • n=7 Participants
|
6672 Steps per day
STANDARD_DEVIATION 4511 • n=5 Participants
|
|
Disability
|
20.8 units on a scale
STANDARD_DEVIATION 6.1 • n=5 Participants
|
21.6 units on a scale
STANDARD_DEVIATION 5.0 • n=7 Participants
|
21.2 units on a scale
STANDARD_DEVIATION 5.7 • n=5 Participants
|
PRIMARY outcome
Timeframe: The first day after hospital dischargeDaily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain (not the average pain) in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Values represent an intercept of modeled worst daily pain on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Intercept
|
8.5 score on a scale
Interval 5.8 to 11.2
|
8.6 score on a scale
Interval 5.9 to 11.3
|
PRIMARY outcome
Timeframe: Postoperative Day 1 through Postoperative Day 60Daily pain intensity report for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. The daily pain intensity was the WORST pain in the past 24 hr on a scale where 0 is no pain and 10 is worst imaginable pain. Slope is defined as change in pain . Values represent the slope of modeled worst daily pain (0-10 scale as described above) divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Pain Between Oxytocin and Placebo--Slope
|
-1.9 Score on a scale
Interval -2.2 to -1.6
|
-2 Score on a scale
Interval -2.3 to -1.7
|
SECONDARY outcome
Timeframe: The first day after hospital dischargeDaily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent an intercept of modeled daily steps on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Intercept
|
144 Daily Steps
Interval -2436.0 to 3527.0
|
546 Daily Steps
Interval -3241.0 to 4332.0
|
SECONDARY outcome
Timeframe: Postoperative Day 1 through Postoperative Day 60Daily steps for each subject were fitted using growth curve model with parameters of intercept (modeled initial steps) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. This is considered as the modeled change in activity listed in the protocol. Values represent the slope of daily steps divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Daily Steps Between Oxytocin and Placebo--Slope
|
562 Daily steps
Interval -130.0 to 1248.0
|
218 Daily steps
Interval -472.0 to 907.0
|
SECONDARY outcome
Timeframe: Modeled WHODAS 2.0 one week after hospital dischargePopulation: The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.
Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent an intercept of modeled WHODAS 2.0 score one week after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Intercept
|
23.2 score on a scale
Interval 9.5 to 41.2
|
29.1 score on a scale
Interval 13.5 to 44.8
|
SECONDARY outcome
Timeframe: Postoperative Day 7 through Postoperative Day 56Population: The estimates were conducted using a linear mixed effects model contrasting differences in the oxytocin group versus placebo. In all cases, these differences are adjusted for prognostic variables including baseline World Health Organization Disability Assessment Score 2.0 value, baseline opioid use, age, sex, baseline PROMIS depression and number of other painful conditions.
Weekly World Health Organization Disability Assessment Score 2.0 (WHODAS 2.0) value for each subject was fitted using growth curve model with parameters of intercept (modeled initial score) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Scale is 12 to 36 with higher scores meaning greater disability. Values represent the slope of WHODAS 2.0 score divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for World Health Organization Disability Assessment Score 2.0 Value Between Oxytocin and Placebo--Slope
|
-7.1 Score on a scale/ln(days)
Interval -11.0 to -3.2
|
-5.6 Score on a scale/ln(days)
Interval -9.5 to -1.7
|
SECONDARY outcome
Timeframe: The first day after hospital dischargeDaily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent an intercept of modeled probability of taking opioid, on a 0-1 probability scale, on the first day after hospital discharge across all participants, extracted from the mixed effect model. The intercept is a number representative of all participants in the Arm and is an estimate with standard deviation based on the model.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Intercept
|
0.9995 Probability of taking opioids
Interval 0.9985 to 1.0005
|
0.9998 Probability of taking opioids
Interval 0.9989 to 1.0007
|
SECONDARY outcome
Timeframe: Postoperative Day 1 through Postoperative Day 60Daily probability of taking opioids for each subject was fitted using growth curve model with parameters of intercept (modeled initial pain) and slope of change in natural log of time, adjusted for prognostic predictors for oxytocin and placebo group separately. Values represent the slope of daily probability of taking opioids divided by the natural log of time (days) across all participants, extracted from the mixed effect model. The slope is a number representative of all participants in the Arm and is an estimate with confidence limits based on the model
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Comparison of Adjusted Trajectory Model for Probability of Taking Opioids Daily Between Oxytocin and Placebo--Slope
|
-0.953 Probability of taking opioids/ln(days)
Interval -0.959 to -0.947
|
-0.787 Probability of taking opioids/ln(days)
Interval -0.799 to -0.775
|
SECONDARY outcome
Timeframe: Preoperative, 2 months after surgeryThis is a computer based card game which assesses risk taking and impulsivity in which a score of -100 to 100 is calculated. Lower numbers indicate greater impulsiivity
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Iowa Gambling Task
Preoperative
|
13 units on a scale
Standard Deviation 30
|
21 units on a scale
Standard Deviation 31
|
|
Iowa Gambling Task
2 Months postoperative
|
20 units on a scale
Standard Deviation 38
|
22 units on a scale
Standard Deviation 37
|
SECONDARY outcome
Timeframe: Preoperative, 2 months after surgeryThis is a physical card sorting game which measures attention to shifts in implicit rules as the game progresses. Perseverative errors are the number of sequential errors when rules of the game shift and reflect dysfunction of attention. This score ranges from 0 to 64 with larger numbers reflecting more dysfunction of attention.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Wisconsin Card Sort Task
Preoperative
|
6.3 units on a scale
Standard Deviation 4.2
|
6.8 units on a scale
Standard Deviation 4.9
|
|
Wisconsin Card Sort Task
2 Months postoperatively
|
8.4 units on a scale
Standard Deviation 4.2
|
7.7 units on a scale
Standard Deviation 6.7
|
SECONDARY outcome
Timeframe: Preoperative, 2 months after surgeryThis 17-question scale assesses the degree of fear of pain from joint movement and is commonly used in orthopedic injury or surgery studies. The scale ranges from 17 to 68 with 17 indicating no fear of movement and 68 indicating severe fear.
Outcome measures
| Measure |
Oxytocin
n=44 Participants
Oxytocin 100 micrograms administered intrathecally
Oxytocin: spinal injection of oxytocin
|
Placebo
n=46 Participants
Placebo injection administered intrathecally
Placebos: spinal injection of placebo
|
|---|---|---|
|
Tampa Scale of Kinesiophobia
Preoperative
|
37 units on a scale
Standard Deviation 4.8
|
38 units on a scale
Standard Deviation 4.6
|
|
Tampa Scale of Kinesiophobia
2 month postoperative
|
36 units on a scale
Standard Deviation 3.8
|
36 units on a scale
Standard Deviation 5.6
|
Adverse Events
Oxytocin
Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Dr. James Eisenach
Wake Forest University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place