Trial Outcomes & Findings for Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids (NCT NCT02977286)
NCT ID: NCT02977286
Last Updated: 2023-02-16
Results Overview
Time to first spontaneous bowel movement during ICU admission after randomization
Recruitment status
TERMINATED
Study phase
PHASE4
Target enrollment
12 participants
Primary outcome timeframe
First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days
Results posted on
2023-02-16
Participant Flow
Participant milestones
| Measure |
Naloxegol Oral Tablet
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna Oral Tablet, Polyethylene Glycols, Magnesium Citrate Oral Liquid Product, Bisacodyl Suppository and Methylnaltrexone\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=6 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=12 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
7 Participants
n=12 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=6 Participants
|
3 Participants
n=6 Participants
|
5 Participants
n=12 Participants
|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 23 • n=6 Participants
|
64 years
STANDARD_DEVIATION 11 • n=6 Participants
|
57 years
STANDARD_DEVIATION 18 • n=12 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=6 Participants
|
4 Participants
n=6 Participants
|
7 Participants
n=12 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=6 Participants
|
2 Participants
n=6 Participants
|
5 Participants
n=12 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
6 participants
n=6 Participants
|
6 participants
n=6 Participants
|
12 participants
n=12 Participants
|
|
BMI
|
40 kg/m2
STANDARD_DEVIATION 13 • n=6 Participants
|
35 kg/m2
STANDARD_DEVIATION 16 • n=6 Participants
|
38 kg/m2
STANDARD_DEVIATION 14 • n=12 Participants
|
|
APACHE-II: Acute Physiology and Chronic Health Evaluation (version II)
|
20 units on a scale
STANDARD_DEVIATION 6 • n=6 Participants
|
19 units on a scale
STANDARD_DEVIATION 7 • n=6 Participants
|
19.5 units on a scale
STANDARD_DEVIATION 6.5 • n=12 Participants
|
|
SOFA score: Sequential Organ Failure Assessment Score
|
8 units on a scale
STANDARD_DEVIATION 4 • n=6 Participants
|
6 units on a scale
STANDARD_DEVIATION 2 • n=6 Participants
|
7 units on a scale
STANDARD_DEVIATION 3 • n=12 Participants
|
|
Hours in ICU before enrollment
|
50 hours
STANDARD_DEVIATION 21 • n=6 Participants
|
44 hours
STANDARD_DEVIATION 21 • n=6 Participants
|
48 hours
STANDARD_DEVIATION 22 • n=12 Participants
|
PRIMARY outcome
Timeframe: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU daysTime to first spontaneous bowel movement during ICU admission after randomization
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Time to First Spontaneous Bowel Movement (SBM) Administration
|
41 hours
Standard Deviation 25
|
33 hours
Standard Deviation 25
|
SECONDARY outcome
Timeframe: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU daysTime to first spontaneous bowel movement during the ICU admission after opioid initiation
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Time to First Spontaneous Bowel Movement (SBM)
|
52 hours
Standard Deviation 28
|
49 hours
Standard Deviation 38
|
SECONDARY outcome
Timeframe: During period of ICU admission or a maximum of 10 ICU daysMeasured ICU days that subjects did not have a SBM
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
ICU Days Without a SBM
|
2 Days
Standard Deviation 3
|
2 Days
Standard Deviation 2
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysMeasurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysAverage daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]
|
1420 mcg per day
Interval 65.0 to 3548.0
|
1600 mcg per day
Interval 1105.0 to 2382.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysConsistency of SBM is characterized in one of 4 categories: hard and formed, soft but formed, loose and unformed, and liquid. The number listed in the results section is the number of patients who had either loose or liquid SBM (as opposed to hard or soft formed).
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Number of Patients With Loose and Unformed or Liquid SBM
|
5 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysA 4-step laxative protocol was initiated when there was no spontaneous bowel movement greater than or equal to 3 days time. Data collected on study laxative protocol included any use as well as the highest level needed.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Number of Patients That Required Use of the Study Laxative Protocol
|
5 participants
|
4 participants
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysEnteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Percentage of Daily Goal Reached for Enteral Nutrition Administration
|
54 percentage of daily goals met
Standard Deviation 34
|
51 percentage of daily goals met
Standard Deviation 29
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysDaily fluid balance measured in mL is the 24 hours ins and outs
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Daily Fluid Balance
|
-338 mL
Interval -747.0 to -102.0
|
-210 mL
Interval -660.0 to -208.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysBased on the highest daily Visual Analogue Scale-10 or Clinical Pain Observation tool assessment. VAS-10 is Visual Analogue Scale which uses a nurse-administered 10 point rating scale. A measurement of 0-1 is minimal pain. A measurement of 10 is severe pain.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Daily Maximal Pain Scale Score
|
0 score on a scale
Interval 0.0 to 3.0
|
0 score on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysThe Sedation Assessment Scale is rated 1 to 7. Score of 7 is dangerous agitation. Score of 1 is unarousable. Score of 2 is very sedated. The presence of coma is based on the every 4 hour sedation agitation score scale (SAS) assessment. A score of 1 or 2 any time during the day represents that a coma is present. A score of 3-7 represents a subject with no coma present. Results listed here is days without coma (SAS score of 3-7)
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Daily Maximal Sedation Assessment Scale (SAS) Score
|
3 days
Interval 1.0 to 3.0
|
7 days
Interval 4.0 to 7.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysMeasures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)
|
5 days without delirium
Interval 4.0 to 6.0
|
6 days without delirium
Interval 4.0 to 7.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge or a maximum of 10 ICU daysNumber of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From ICU admission to ICU discharge or a maximum of 10 ICU daysMeasure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Days Without Mechanical Ventilation Support for Duration of ICU Stay
|
0.5 days
Interval 0.2 to 5.0
|
1 days
Interval 0.3 to 3.0
|
SECONDARY outcome
Timeframe: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU daysOn days when the patient had a urinary catheter in place for clinical reasons, a bladder pressure transducer was inserted and abdominal pressure was measured. The average daily maximum pressure score for each group is reported.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=4 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Abdominal Pressure Measurement
|
10 mmHg
Standard Deviation 4
|
13 mmHg
Standard Deviation 5
|
SECONDARY outcome
Timeframe: Study drug initiation to first episode of diarrhea in hours.Population: Number of patients in each group with \> or equal to 1 episode of diarrhea.
The number of patients in each group with \> or equal to 1 episode of diarrhea after initiation of study drug. The time to first episode of diarrhea was measured in hours.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=4 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=4 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Time to First Episode of Diarrhea
|
40 hours
Interval 19.0 to 66.0
|
109 hours
Interval 48.0 to 169.0
|
SECONDARY outcome
Timeframe: One hour before the daily study drug administration and 2 hours after the daily study drug administrationPatients were evaluated 1 hour before and 2 hours after the administration of each dose of study medication using the Clinical Opioid Withdrawal Scale (COWS). COWS is used to help determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. The COWS score ranges from 0-36+. A score of 0 is no active opioid withdrawal. A score of 5-12 is mild; 13-24 is moderate; 25-36 is moderately severe and more than 36 is severe opioid withdrawal.
Outcome measures
| Measure |
Naloxegol Oral Tablet
n=6 Participants
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 Participants
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score
|
-0.1 Difference of COWS score
Standard Deviation 1.3
|
0.2 Difference of COWS score
Standard Deviation 1.3
|
Adverse Events
Naloxegol Oral Tablet
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Placebo Oral Tablet
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Naloxegol Oral Tablet
n=6 participants at risk
Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: Movantik
|
Placebo Oral Tablet
n=6 participants at risk
Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily \[that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)\] until one of the following:
1. Adverse event potentially attributable to the study drug.
2. Use of Relistor.
3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
4. The participant has been administered 10 days of study medication.
5. The participant is discharged from the ICU.
6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.
Other Name: AstraZeneca provided Movantik placebo
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
66.7%
4/6 • Adverse event data was collected for each subject during the period from time of study enrollment (i.e. randomization) to ICU discharge, death or 10 days of study drug administration (whatever comes first).
|
66.7%
4/6 • Adverse event data was collected for each subject during the period from time of study enrollment (i.e. randomization) to ICU discharge, death or 10 days of study drug administration (whatever comes first).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place