Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids

NCT02977286 | Terminated Phase 4 Results DMC

• 1 other identifier: 11200
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the participants will receive naloxegol and a laxative protocol and half the participants will receive a placebo and a laxative protocol.

Conditions

Constipation

Outcome Measures

Primary Outcomes (1)

• 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 (16)

• Time to First Spontaneous Bowel Movement (SBM)

  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

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

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

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

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

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

• Number of Patients With Loose and Unformed or Liquid SBM

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

Study Arms (2)

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: 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

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: 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

Drug: Placebo 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

Interventions

Naloxegol Oral Tablet DRUG

Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily

Also known as: Movantik

Naloxegol Oral Tablet

Placebo Oral Tablet DRUG

Placebo Oral Tablet po (enteral) twice daily

Also known as: Official AstraZeneca placebo for Movantik

Placebo Oral Tablet

Docusate Sodium 100 Mg oral capsule [Colace] DRUG

Docusate Sodium 100 mg po (enteral) twice daily

Also known as: Colace

Naloxegol Oral Tablet; Placebo Oral Tablet

Senna 217 Mg Oral Tablet DRUG

Senna 127 mg oral tablet daily if no spontaneous bowel movement \>/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement \>/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement \>/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement \>/=6 days after scheduled opioid initiation.

Also known as: Senokot

Naloxegol Oral Tablet; Placebo Oral Tablet

Polyethylene Glycols DRUG

Polyethylene Glycols 17 g daily if no spontaneous bowel movement \>/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement \>/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement \>/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement \>/= 6 days after scheduled opioid initiation.

Also known as: Miralax

Naloxegol Oral Tablet; Placebo Oral Tablet

Bisacodyl 10 mg Suppository DRUG

Insert one suppository if no spontaneous bowel movement \>/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement \>/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement \>/= 6 days after scheduled opioid initiation.

Also known as: Dulcolax

Naloxegol Oral Tablet; Placebo Oral Tablet

Magnesium Citrate Oral Liquid Product DRUG

Administer one 10 oz bottle if no spontaneous bowel movement \>/= 5 days after scheduled opioid initiation.

Also known as: Citromag

Naloxegol Oral Tablet; Placebo Oral Tablet

Methylnaltrexone DRUG

Administer 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement \>/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication.

Also known as: Relistor

Naloxegol Oral Tablet; Placebo Oral Tablet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Admitted to an ICU
• Expected to require admission to an ICU for ≥ 48 hours
• Intravenous opioid administration in the prior 24 hours of ≥ 100 mcg fentanyl equivalents

You may not qualify if:

• Scheduled use of an opioid ≥ 10 mg morphine equivalents per day in the week prior to ICU admission
• History of constipation (≤ 2 SBM per week and current use of stool softener or laxative therapy) prior to ICU admission
• Current scheduled use of a medication affecting gastric motility
• Current use of a medication known to be a strong CYP3A4 inhibitor
• History of a neurologic condition that may affect the permeability of the blood-brain barrier
• Acute GI condition (e.g., clinical evidence of acute fecal impaction/complete obstruction, acute surgical abdomen, acute GI bleeding)
• Condition affecting GI motility or function (e.g. inflammatory bowel disease requiring immunosuppressive therapy, symptomatic Clostridium difficile, active diverticular disease, surgery on the colon or abdomen within 60 days of ICU admission)
• Current use of total parenteral nutrition
• Administration of enteral nutrition through a jejunal tube
• Severe hepatic dysfunction
• Endstage renal disease defined as either i. calculated creatinine clearance ≤ 10ml/min or ii. Any current use of renal replacement therapy
• Inability to enroll in study and initiate study medication within 48 hours of the patient begin first initiated on scheduled IV opioid therapy after ICU admission
• Unreliable method for enteral, gastric and/or oral medication administration (e.g., no feeding tube, nasogastric tube is on suction)
• Current or previous use of an opioid antagonist agent (e.g., naloxegol, methylnaltrexone) in the past 30 days
• Pregnant or actively lactating females

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Related Publications (2)

• 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.

  PMID: 22310869 BACKGROUND

• de Azevedo RP, Freitas FG, Ferreira EM, Pontes de Azevedo LC, Machado FR. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Crit Care. 2015 Sep 16;19(1):329. doi: 10.1186/s13054-015-1047-x.

  PMID: 26373705 BACKGROUND

MeSH Terms

Conditions

Constipation

Interventions

naloxegol; Dioctyl Sulfosuccinic Acid; Sennosides; Tablets; Polyethylene Glycols; polyethylene glycol 3350; Bisacodyl; Suppositories; magnesium citrate; methylnaltrexone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Succinates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Senna Extract; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Polycyclic Compounds; Glycosides; Carbohydrates; Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Ethylene Glycols; Glycols; Alcohols; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Cresols; Phenols; Benzene Derivatives

Limitations and Caveats

Limitations: One-third of the planned participants were enrolled, thus the study is substantially underpowered. Our results do not apply to non-medical patients.

Results Point of Contact

• Title: Erik Garpestad, M.D.
• Organization: Tufts Medical Center

egarpestad@tuftsmedicalcenter.org

617-636-5388

Study Officials

• Erik Garpestad, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2016
• First Posted: November 30, 2016
• Study Start: January 1, 2017
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: February 16, 2023
• Results First Posted: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)