Trial Outcomes & Findings for Ancillary Effects of Oral Naloxegol (Movantik) (NCT NCT03235739)
NCT ID: NCT03235739
Last Updated: 2023-09-05
Results Overview
Residual urine volume in the bladder as assessed by bladder scan
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
136 participants
Primary outcome timeframe
from Postoperative days 1 to POD 2 or until day of discharge whichever occurs first
Results posted on
2023-09-05
Participant Flow
of 508 patients screened, 136 patients meet all inclusion and exclusion criteria and gave consent to the study. 136 patients were randomized.
Participant milestones
| Measure |
Treatment-Naloxegol
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Overall Study
STARTED
|
69
|
67
|
|
Overall Study
COMPLETED
|
67
|
64
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Treatment-Naloxegol
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
|
Overall Study
Physician Decision
|
0
|
1
|
Baseline Characteristics
one patient was missing on anesthesia type information
Baseline characteristics by cohort
| Measure |
Treatment-Naloxegol
n=67 Participants
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=64 Participants
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
Total
n=131 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64 years
STANDARD_DEVIATION 13 • n=67 Participants
|
62 years
STANDARD_DEVIATION 11 • n=64 Participants
|
63 years
STANDARD_DEVIATION 12 • n=131 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=67 Participants
|
32 Participants
n=64 Participants
|
64 Participants
n=131 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=67 Participants
|
32 Participants
n=64 Participants
|
67 Participants
n=131 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
59 Participants
n=67 Participants
|
57 Participants
n=64 Participants
|
116 Participants
n=131 Participants
|
|
Race/Ethnicity, Customized
African American
|
6 Participants
n=67 Participants
|
5 Participants
n=64 Participants
|
11 Participants
n=131 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=67 Participants
|
0 Participants
n=64 Participants
|
1 Participants
n=131 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
1 Participants
n=67 Participants
|
2 Participants
n=64 Participants
|
3 Participants
n=131 Participants
|
|
ASA status
1
|
1 Participants
n=67 Participants
|
1 Participants
n=64 Participants
|
2 Participants
n=131 Participants
|
|
ASA status
2
|
8 Participants
n=67 Participants
|
15 Participants
n=64 Participants
|
23 Participants
n=131 Participants
|
|
ASA status
3
|
52 Participants
n=67 Participants
|
46 Participants
n=64 Participants
|
98 Participants
n=131 Participants
|
|
ASA status
4
|
6 Participants
n=67 Participants
|
2 Participants
n=64 Participants
|
8 Participants
n=131 Participants
|
|
Apfel PONV score
|
2 units on a scale
n=67 Participants
|
2 units on a scale
n=64 Participants
|
2 units on a scale
n=131 Participants
|
|
Chronic opioid use
|
36 Participants
n=67 Participants
|
32 Participants
n=64 Participants
|
68 Participants
n=131 Participants
|
|
Surgery type
Hip
|
67 Participants
n=67 Participants
|
64 Participants
n=64 Participants
|
131 Participants
n=131 Participants
|
|
Surgery type
Knee
|
0 Participants
n=67 Participants
|
0 Participants
n=64 Participants
|
0 Participants
n=131 Participants
|
|
Surgery duration
|
3.6 hours
n=67 Participants
|
3.5 hours
n=64 Participants
|
3.6 hours
n=131 Participants
|
|
Medical history
Kidney disease
|
4 Participants
n=67 Participants
|
1 Participants
n=64 Participants
|
5 Participants
n=131 Participants
|
|
Medical history
chronic pulmonary disease
|
9 Participants
n=67 Participants
|
9 Participants
n=64 Participants
|
18 Participants
n=131 Participants
|
|
Medical history
obstructive sleep apnea
|
9 Participants
n=67 Participants
|
6 Participants
n=64 Participants
|
15 Participants
n=131 Participants
|
|
Medical history
diabetes mellitus
|
7 Participants
n=67 Participants
|
7 Participants
n=64 Participants
|
14 Participants
n=131 Participants
|
|
Medical history
myocardial infarction
|
6 Participants
n=67 Participants
|
4 Participants
n=64 Participants
|
10 Participants
n=131 Participants
|
|
Medical history
Ischemic Heart Disease
|
14 Participants
n=67 Participants
|
10 Participants
n=64 Participants
|
24 Participants
n=131 Participants
|
|
Medical history
neurological disease
|
7 Participants
n=67 Participants
|
12 Participants
n=64 Participants
|
19 Participants
n=131 Participants
|
|
Medical history
chronic pain
|
1 Participants
n=67 Participants
|
5 Participants
n=64 Participants
|
6 Participants
n=131 Participants
|
|
Medical history
current smoker
|
9 Participants
n=67 Participants
|
7 Participants
n=64 Participants
|
16 Participants
n=131 Participants
|
|
Medical history
drug user
|
2 Participants
n=67 Participants
|
5 Participants
n=64 Participants
|
7 Participants
n=131 Participants
|
|
Medical history
alcohol abuse
|
10 Participants
n=67 Participants
|
7 Participants
n=64 Participants
|
17 Participants
n=131 Participants
|
|
Medical history
cancer
|
10 Participants
n=67 Participants
|
6 Participants
n=64 Participants
|
16 Participants
n=131 Participants
|
|
Anesthesia type
General anesthesia
|
46 Participants
n=67 Participants • one patient was missing on anesthesia type information
|
45 Participants
n=63 Participants • one patient was missing on anesthesia type information
|
91 Participants
n=130 Participants • one patient was missing on anesthesia type information
|
|
Anesthesia type
Spinal anesthesia
|
21 Participants
n=67 Participants • one patient was missing on anesthesia type information
|
18 Participants
n=63 Participants • one patient was missing on anesthesia type information
|
39 Participants
n=130 Participants • one patient was missing on anesthesia type information
|
|
Intraoperative colloids, ml
|
0 ml
n=67 Participants • one patient was missing on colloids information
|
0 ml
n=63 Participants • one patient was missing on colloids information
|
0 ml
n=130 Participants • one patient was missing on colloids information
|
|
Intraoperative crystalloids
|
2000 ml
n=67 Participants • one patient was missing on crystalloids
|
1800 ml
n=63 Participants • one patient was missing on crystalloids
|
1900 ml
n=130 Participants • one patient was missing on crystalloids
|
|
Intraoperative RBC
|
0 cc
n=67 Participants • one patient was missing
|
0 cc
n=63 Participants • one patient was missing
|
0 cc
n=130 Participants • one patient was missing
|
|
Intraoperative platelets
|
0 cc
n=67 Participants • one patient was missing
|
0 cc
n=63 Participants • one patient was missing
|
0 cc
n=130 Participants • one patient was missing
|
|
intraoperative Urine
|
0 cc
n=67 Participants • one patient was missing
|
0 cc
n=63 Participants • one patient was missing
|
0 cc
n=130 Participants • one patient was missing
|
|
Intraoperative opioid use
|
20 mg
n=67 Participants • one patient was missing
|
20 mg
n=63 Participants • one patient was missing
|
20 mg
n=130 Participants • one patient was missing
|
PRIMARY outcome
Timeframe: from Postoperative days 1 to POD 2 or until day of discharge whichever occurs firstPopulation: 17 patients were completely missing on urine residual. Multiple imputation was used solely for estimating the treatment effect on urinal residual. The summary statistics of urine residual for each day was reported based on original data.
Residual urine volume in the bladder as assessed by bladder scan
Outcome measures
| Measure |
Treatment-Naloxegol
n=59 Participants
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=55 Participants
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Residual Urine Volume
Day 1 AM
|
62 ml
Interval 5.0 to 187.0
|
114 ml
Interval 13.0 to 247.0
|
|
Residual Urine Volume
Day 1 PM
|
48 ml
Interval 0.0 to 206.0
|
31 ml
Interval 0.0 to 169.0
|
|
Residual Urine Volume
Day 2 AM
|
32 ml
Interval 0.0 to 152.0
|
28 ml
Interval 0.0 to 122.0
|
|
Residual Urine Volume
Day 2 PM
|
0 ml
Interval 0.0 to 122.0
|
28 ml
Interval 0.0 to 66.0
|
SECONDARY outcome
Timeframe: Postoperative days 1-2 or until day of discharge whichever occurs firstPopulation: some patients were missing on this outcome at repeated measurements. A mixed effects model assuming auto-regressive correlation structure and the outcome was log-transformed
Opioid-related Symptom Distress Scale (ORSDS) is a 4 point-scale that evaluates three symptom distress dimensions (frequency, severity, bothersomeness) for opioid-related side effects. The 12 elements of the ORSDS are nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness, lightheaded, fatigue, feeling confused, itchiness, dry mouth, and headache. The ORSDS questionnaire was administered by a trained investigator on first and second postoperative days while patients remained hospitalized. We reported the average ORSDS score from all 12 elements, which ranged from 0 to 4 and higher scores represent worse outcome.
Outcome measures
| Measure |
Treatment-Naloxegol
n=66 Participants
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=61 Participants
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Side Effects of Naloxegol on Other Opioid Related Side Effects
Day 1
|
0.53 log(score on a scale)
Interval 0.34 to 0.79
|
0.45 log(score on a scale)
Interval 0.31 to 0.81
|
|
Side Effects of Naloxegol on Other Opioid Related Side Effects
Day 2
|
0.34 log(score on a scale)
Interval 0.2 to 0.64
|
0.34 log(score on a scale)
Interval 0.13 to 0.62
|
SECONDARY outcome
Timeframe: Postoperative days 1-2 or until day of discharge whichever occurs firstPopulation: Our final analyzed study population had 131 patients since 5 patients did not complete (due to withdrawal or not receiving any treatment) the study thus were removed from the final analysis. Among 131 patients, 4 patients were missing from this analysis.
Number of patients receiving Naloxegol requiring indwelling urinary catheters
Outcome measures
| Measure |
Treatment-Naloxegol
n=65 Participants
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=62 Participants
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Need for Indwelling Urinary Catheterization
|
19 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Postoperative Days 2 or discharge day whichever was earlierPopulation: We only had a total of 131 patients in our final analysis since 5 patients were removed from the final analysis due to not completing the study (withdrawal or not receiving any treatment). Among 131 patients, 9 patients were missing from this analysis
Quality of recovery is a validated scoring system that quantifies patients' early postoperative health status with range of 0-150 where higher score means better quality of recovery. We used the 15-question version, the QoR-15
Outcome measures
| Measure |
Treatment-Naloxegol
n=63 Participants
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=59 Participants
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Quality of Recovery
|
119 units on a scale
Interval 103.0 to 131.0
|
123 units on a scale
Interval 115.0 to 133.0
|
Adverse Events
Treatment-Naloxegol
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Placebo Arm
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment-Naloxegol
n=67 participants at risk
Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Naloxegol 25 MG: Oral Naloxegol 25 MG
|
Placebo Arm
n=64 participants at risk
Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first
Placebo: matching oral placebo
|
|---|---|---|
|
Cardiac disorders
Troponin elevation and ST elevation
|
1.5%
1/67 • Number of events 1 • until discharge from hospital, an average of 2 day, up to 3 days
Adverse events of particular interest are: * Opioid withdrawal: hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability * Severe abdominal pain (\>8/10) and/or diarrhea * Gastrointestinal perforation
|
0.00%
0/64 • until discharge from hospital, an average of 2 day, up to 3 days
Adverse events of particular interest are: * Opioid withdrawal: hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability * Severe abdominal pain (\>8/10) and/or diarrhea * Gastrointestinal perforation
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place