The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit (NaRC-ICU)

April 30, 2021 updated by: Massachusetts General Hospital
Naloxegol has recently been approved by the US Food and Drug Administration to treat opioid induced constipation in non-cancer chronic pain patients. Its effectiveness in acute care patients, however, is not known. Therefore, the researchers' goal is to investigate whether naloxegol is superior to osmotic laxatives for refractory constipation in ICU patients already receiving prophylactic stool softeners and simulant laxatives through a double-blind, randomized control trial.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Constipation is often defined as the absence of a bowel movement for 3 consecutive days. The incidence of constipation in critically ill patients is estimated to be 50-80%. Constipation in the ICU is associated with various undesirable clinical outcomes, including: increased rate of infections, prolonged duration of mechanical ventilation, greater hospital length of stay, worsening of organ dysfunction, and even higher mortality.

Typical first-line agents for the management of ICU constipation include stool softeners (e.g. docusate) and bowel stimulants (e.g. senna glycol or bisacodyl), and these are often used prophylactically in critically ill patients. However, a significant proportion of patients require additional therapy to promote laxation , the most common being osmotic agents such as propylene glycol or lactulose. Often, multiple doses of osmotic agents over several days are required to achieve acceptable laxation rates during critical illness. As such, this has prompted the need for targeted therapy to improve constipation in the ICU.

Among major risk factors for constipation in the ICU are the lack of bowel stimulation via nutrition and exposure to high doses of continuous opioids . Indeed, clinical data suggests that early enteral nutrition promotes laxation in ICU patients. And recently, methylnaltrexone, a peripherally acting μ-opioid receptor antagonist, has shown promising results in its ability to reverse opioid-induced constipation. However, methylnaltrexone is delivered via subcutaneous injection and its absorption is likely to be variable in critically ill patients who often receive aggressive fluid resuscitation and have significant peripheral edema. The US Food and Drug Administration recently approved the use of naloxegol, a μ-opioid receptor antagonist available in tablet form, for the management of opioid-induced constipation in non-cancer chronic pain patients.

Study Type

Interventional

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥18 years
  2. Admitted to an ICU at Massachusetts General Hospital (MGH)
  3. Received ≥72 hours of continuous opioid infusion
  4. Anticipated to require ≥48 hours of additional care in the ICU
  5. Did not have a bowel movement in ≥72 hours
  6. Allowed to receive (and tolerating) medications via nasogastric, orogastric, gastric, gastrojejunal, or oral route
  7. Receiving at least trophic (10 mL/hr) of enteral nutrition

Exclusion Criteria:

  1. Unable to provide informed consent or unavailable healthcare proxy
  2. Not expected to survive >48 hours from time of enrollment
  3. "Comfort measures only" status (i.e. palliative care)
  4. Received medication other that docusate and senna glycoside for laxation
  5. Had abdominal surgery that is expected to cause significant ileus
  6. Mechanical bowel obstruction
  7. Total bowel rest/exclusively receiving total parenteral nutrition
  8. History of chronic constipation unrelated to opioid use
  9. Compromised blood-brain-barrier
  10. Current diagnosis of solid organ or hematologic cancer
  11. On moderate/strong CYP3A4 inhibitors or strong CYP3A4 inducers
  12. On other opioid antagonists
  13. Pregnant or lactating females

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Polyethylene glycol
17g power qday; reconstituted in water for naso/orogastric tube administration
Drug: Polyethylene glycol
Intervention would be given by oro-gastric (OG) or naso-gastric (NG) tube
Other Names:
  • Polyethylene glycol (PEG)
  • miralax
  • glycolax
Experimental: naloxegol
25mg qday; crushed pill reconstituted in water for naso/orogastric tube administration
Drug: naloxegol
Intervention would be given by OG or NG tube
Other Names:
  • Movantik

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Laxation within 48 hours of starting second-line agent
Time Frame: From 72 hours after ICU admission until 120 hours after ICU admission
Documented bowel movement (Yes/No) within 48 hours of randomization to receive second-line laxative agent
From 72 hours after ICU admission until 120 hours after ICU admission

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to first bowel movement after starting second-line agent
Time Frame: From 72 hours after ICU admission until 120 hours after ICU admission
Number of hours from initiation of a second-line laxative agent until first documented bowel movement
From 72 hours after ICU admission until 120 hours after ICU admission
Doses of second-line laxative agent before bowel movement
Time Frame: From 72 hours after ICU admission until 120 hours after ICU admission
Number of doses of second-line laxative agent until first documented bowel movement
From 72 hours after ICU admission until 120 hours after ICU admission
Protein/caloric deficit
Time Frame: From admission to the ICU until the end of day 7 after ICU admission
Cumulative calorie and protein deficits will be calculated in kcals and grams, respectively, utilizing standard clinical formulas from the day of ICU admission until day 7 of ICU admission
From admission to the ICU until the end of day 7 after ICU admission
Feeding interruptions
Time Frame: From admission to the ICU until the end of day 7 after ICU admission
Number of interruptions to enteral nutrition for high gastric residual volume during study period
From admission to the ICU until the end of day 7 after ICU admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

AstraZeneca

Investigators

  • Principal Investigator: Sadeq A. Quraishi, MD,MHA,MMSc, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 1, 2017

Primary Completion (Anticipated)

April 1, 2019

Study Completion (Anticipated)

December 1, 2019

Study Registration Dates

First Submitted

February 5, 2016

First Submitted That Met QC Criteria

March 4, 2016

First Posted (Estimate)

March 10, 2016

Study Record Updates

Last Update Posted (Actual)

May 5, 2021

Last Update Submitted That Met QC Criteria

April 30, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NaRC-ICU_temp

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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