Naloxegol to Prevent Lower Gastrointestinal Paralysis in... | NCT02977286

NCT02977286

Status Module

Oversight Module

Description Module

Detailed Description

Among the more than 5 million adults who are admitted to the ICU each year in the USA, most have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in critically ill adults continues to increase given the greater awareness of untreated pain in the ICU and that an opioid-first approach be used to optimize patient safety and comfort and improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability to pass stool due to impaired gut movement, and is a common effect of opioid use in the critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise the ability to administer tube feeds (enteral nutrition), an increase abdominal pain, delirium and delay getting off mechanical ventilation. One recent randomized study found that aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was associated with lower daily organ dysfunction [as measured by the Sequential Organ Failure Assessment (SOFA) score]. The lower GI tract paralysis that occurs in the critically ill often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose). While stool softener medications like docusate are routinely administered to patients on opioids, laxative-based protocols are frequently not initiated in the ICU until signs of lower GI tract paralysis start to appear. There is therefore an important and unmet need for a safe and efficacious medication to prevent lower GI tract paralysis in critically ill adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the brain (and therefore does not block the pain effects of opioids). Naloxegol is currently approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy, convenience of administration, and safety profile that make it an ideal candidate for use as a preventative medication for lower GI tract paralysis in critically ill adults receiving scheduled opioid therapy. The investigators propose a pilot study in which they will test the hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis in critically ill adults initiated on scheduled IV opioid therapy, and its use will not result in side effects that are concerning to doctors or patients. The investigators will randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or 12.5mg (in patients with a creatinine clearance ≤ 60ml/min)] or placebo. This pilot study will provide valuable information to help guide future, larger studies evaluating the role of naloxegol in critically ill adults.

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Naloxegol Oral Tablet	Experimental	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik	Drug: Naloxegol Oral Tablet Drug: Docusate Sodium 100 Mg oral capsule [Colace] Drug: Senna 217 Mg Oral Tablet Drug: Polyethylene Glycols Drug: Bisacodyl 10 mg Suppository Drug: Magnesium Citrate Oral Liquid Product Drug: Methylnaltrexone
Placebo Oral Tablet	Placebo Comparator	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo	Drug: Placebo Oral Tablet Drug: Docusate Sodium 100 Mg oral capsule [Colace] Drug: Senna 217 Mg Oral Tablet

Name	Type	Description	Arm Group Labels	Other Names
Naloxegol Oral Tablet	Drug	Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily	Naloxegol Oral Tablet

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to First Spontaneous Bowel Movement (SBM) Administration	Time to first spontaneous bowel movement during ICU admission after randomization	First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days

Secondary Outcomes

Measure	Description	Time Frame
Time to First Spontaneous Bowel Movement (SBM)	Time to first spontaneous bowel movement during the ICU admission after opioid initiation	First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days
ICU Days Without a SBM

Eligibility Module

Name	Affiliation	Role
Erik Garpestad, MD	Tufts Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Tufts Medical Center		Boston	Massachusetts	02111	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
22310869	Background	Reintam Blaser A, Malbrain ML, Starkopf J, Fruhwald S, Jakob SM, De Waele J, Braun JP, Poeze M, Spies C. Gastrointestinal function in intensive care patients: terminology, definitions and management. Recommendations of the ESICM Working Group on Abdominal Problems. Intensive Care Med. 2012 Mar;38(3):384-94. doi: 10.1007/s00134-011-2459-y. Epub 2012 Feb 7.
26373705

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 10, 2018	Nov 14, 2021

Arm/Group Information

ID	Title	Description
BG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
BG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG00212

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG00041± 25 OG00133± 25

Secondary

Time to First Spontaneous Bowel Movement (SBM)

Time to first spontaneous bowel movement during the ICU admission after opioid initiation

Posted

Mean

Standard Deviation

hours

First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

ICU Days Without a SBM

Measured ICU days that subjects did not have a SBM

Posted

Mean

Standard Deviation

Days

During period of ICU admission or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik .
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Occurrence of Lower GI Tract Paralysis (≥3 Days Without a SBM)

Measurement is the number of subjects in each group having this occurrence of lower GI tract paralysis during time frame

Posted

Count of Participants

Participants

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Average Daily Opioid Requirement [in IV Fentanyl Equivalents (mcg Per Day)]

Average daily opioid requirement is converted to IV fentanyl equivalent listed in mcg per day

Posted

Mean

Inter-Quartile Range

mcg per day

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Number of Patients With Loose and Unformed or Liquid SBM

Consistency 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).

Posted

Count of Participants

Participants

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Number of Patients That Required Use of the Study Laxative Protocol

A 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.

Posted

Number

participants

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Percentage of Daily Goal Reached for Enteral Nutrition Administration

Enteral nutrition is assessed as daily volume in mL and the reported measure is the percentage of daily goal of enteral nutrition met.

Posted

Mean

Standard Deviation

percentage of daily goals met

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Daily Fluid Balance

Daily fluid balance measured in mL is the 24 hours ins and outs

Posted

Mean

Inter-Quartile Range

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Daily Maximal Pain Scale Score

Based 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.

Posted

Mean

Inter-Quartile Range

score on a scale

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo ation.

Secondary

Daily Maximal Sedation Assessment Scale (SAS) Score

The 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)

Posted

Median

Inter-Quartile Range

days

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Daily Presence of Delirium Using the Intensive Care Delirium Screening Checklist (ICDSC)

Measures as days without delirium with daily presence of delirium assessed using the Intensive Care Delirium Screening Checklist (ICDSC)

Posted

Median

Inter-Quartile Range

days without delirium

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Occurrence of Lower GI Tract Paralysis Requiring GI/Surgical Consultation

Number of patients with GI tract paralysis requiring Gastroenterology service or Surgical service consultation

Posted

Count of Participants

Participants

From randomization to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Days Without Mechanical Ventilation Support for Duration of ICU Stay

Measure is days without mechanical ventilation for duration of ICU stay as expressed as median and inter-Quartile Range

Posted

Median

Inter-Quartile Range

days

From ICU admission to ICU discharge or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Abdominal Pressure Measurement

On 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.

Posted

Mean

Standard Deviation

mmHg

From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Time to First 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.

Number of patients in each group with > or equal to 1 episode of diarrhea.

Posted

Median

Inter-Quartile Range

hours

Study drug initiation to first episode of diarrhea in hours.

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo

Secondary

Daily Difference in the Pre-dose and Post-dose Clinical Opioid Withdrawal Scale (COWS) Score

Patients 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.

Posted

Mean

Standard Deviation

Difference of COWS score

One hour before the daily study drug administration and 2 hours after the daily study drug administration

ID	Title	Description
OG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik
OG001	Placebo Oral Tablet

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Naloxegol Oral Tablet	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: Movantik	0	6	0	6	4	6
EG001	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: Adverse event potentially attributable to the study drug. Use of Relistor. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment. The participant has been administered 10 days of study medication. The participant is discharged from the ICU. The participant requires the initiation of a strong CYP3A4 inhibitor medication. Other Name: AstraZeneca provided Movantik placebo	0	6	0	6	4	6

Ancestor Terms

ID	Term
D013386	Succinates
D003998	Dicarboxylic Acids
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D012676	Senna Extract
D000880	Anthraquinones
D000095322	Anthrones
D000873	Anthracenes
D011084	Polycyclic Aromatic Hydrocarbons
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D011809	Quinones
D011083	Polycyclic Compounds
D006027	Glycosides
D002241	Carbohydrates
D010936	Plant Extracts
D028321	Plant Preparations
D001688	Biological Products
D045424	Complex Mixtures
D004304	Dosage Forms
D004364	Pharmaceutical Preparations
D005026	Ethylene Glycols
D006018	Glycols
D000438	Alcohols
D011108	Polymers
D046911	Macromolecular Substances
D001697	Biomedical and Dental Materials
D008420	Manufactured Materials
D013676	Technology, Industry, and Agriculture
D003408	Cresols
D010636	Phenols
D001555	Benzene Derivatives

ID	Term
D012817	Signs and Symptoms, Digestive
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
C000589308	naloxegol
D004143	Dioctyl Sulfosuccinic Acid
D000081226	Sennosides
D013607	Tablets
D011092	Polyethylene Glycols
C000595212	polyethylene glycol 3350
D001726	Bisacodyl
D013488	Suppositories
C110422	magnesium citrate
C032257	methylnaltrexone