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

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ClinicalTrials.gov Identifier: NCT02705378
Recruitment Status : Not yet recruiting
First Posted : March 10, 2016
Last Update Posted : March 30, 2017
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Sadeq A. Quraishi, Massachusetts General Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Constipation Critical Illness Drug: Polyethylene glycol Drug: naloxegol Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit
Estimated Study Start Date : May 2017
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

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 Name: Movantik




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02705378


Contacts
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Contact: Sadeq A. Quraishi, MD,MHA,MMSc 617-643-5430 SQURAISHI@mgh.harvard.edu
Contact: Tiffany M Otero, BS 617-643-5430 totero@partners.org

Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
AstraZeneca
Investigators
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Principal Investigator: Sadeq A. Quraishi, MD,MHA,MMSc Massachusetts General Hospital

Additional Information:
Publications:

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Responsible Party: Sadeq A. Quraishi, Critical Care Intensivist, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02705378     History of Changes
Other Study ID Numbers: NaRC-ICU_temp
First Posted: March 10, 2016    Key Record Dates
Last Update Posted: March 30, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sadeq A. Quraishi, Massachusetts General Hospital:
Intensive care unit
ICU
Critical Illness
Constipation

Additional relevant MeSH terms:
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Constipation
Critical Illness
Signs and Symptoms, Digestive
Signs and Symptoms
Disease Attributes
Pathologic Processes
Naloxegol
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents