The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit

NCT02705378 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: NaRC-ICU_temp
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Constipation; Critical Illness

Keywords

Intensive care unit; ICU; Critical Illness; Constipation

Outcome Measures

Primary Outcomes (1)

• Laxation within 48 hours of starting second-line agent

  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 Outcomes (4)

• Time to first bowel movement after starting second-line agent

  From 72 hours after ICU admission until 120 hours after ICU admission

• Doses of second-line laxative agent before bowel movement

  From 72 hours after ICU admission until 120 hours after ICU admission

• Protein/caloric deficit

  From admission to the ICU until the end of day 7 after ICU admission

• Feeding interruptions

  From admission to the ICU until the end of day 7 after ICU admission

Study Arms (2)

Polyethylene glycol

ACTIVE COMPARATOR

17g power qday; reconstituted in water for naso/orogastric tube administration

Drug: Polyethylene glycol

naloxegol

EXPERIMENTAL

25mg qday; crushed pill reconstituted in water for naso/orogastric tube administration

Drug: naloxegol

Interventions

Polyethylene glycol DRUG

Intervention would be given by oro-gastric (OG) or naso-gastric (NG) tube

Also known as: Polyethylene glycol (PEG), miralax, glycolax

Polyethylene glycol

naloxegol DRUG

Intervention would be given by OG or NG tube

Also known as: Movantik

naloxegol

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 at Massachusetts General Hospital (MGH)
• Received ≥72 hours of continuous opioid infusion
• Anticipated to require ≥48 hours of additional care in the ICU
• Did not have a bowel movement in ≥72 hours
• Allowed to receive (and tolerating) medications via nasogastric, orogastric, gastric, gastrojejunal, or oral route
• Receiving at least trophic (10 mL/hr) of enteral nutrition

You may not qualify if:

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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• AstraZeneca: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (13)

• Patanwala AE, Abarca J, Huckleberry Y, Erstad BL. Pharmacologic management of constipation in the critically ill patient. Pharmacotherapy. 2006 Jul;26(7):896-902. doi: 10.1592/phco.26.7.896.

  PMID: 16803421 BACKGROUND

• Mostafa SM, Bhandari S, Ritchie G, Gratton N, Wenstone R. Constipation and its implications in the critically ill patient. Br J Anaesth. 2003 Dec;91(6):815-9. doi: 10.1093/bja/aeg275.

  PMID: 14633751 BACKGROUND

• van der Spoel JI, Oudemans-van Straaten HM, Kuiper MA, van Roon EN, Zandstra DF, van der Voort PH. Laxation of critically ill patients with lactulose or polyethylene glycol: a two-center randomized, double-blind, placebo-controlled trial. Crit Care Med. 2007 Dec;35(12):2726-31. doi: 10.1097/01.CCM.0000287526.08794.29.

  PMID: 17893628 BACKGROUND

• Nassar AP Jr, da Silva FM, de Cleva R. Constipation in intensive care unit: incidence and risk factors. J Crit Care. 2009 Dec;24(4):630.e9-12. doi: 10.1016/j.jcrc.2009.03.007. Epub 2009 Jul 9.

  PMID: 19592200 BACKGROUND

• Gacouin A, Camus C, Gros A, Isslame S, Marque S, Lavoue S, Chimot L, Donnio PY, Le Tulzo Y. Constipation in long-term ventilated patients: associated factors and impact on intensive care unit outcomes. Crit Care Med. 2010 Oct;38(10):1933-8. doi: 10.1097/CCM.0b013e3181eb9236.

  PMID: 20639749 BACKGROUND

• van der Spoel JI, Schultz MJ, van der Voort PH, de Jonge E. Influence of severity of illness, medication and selective decontamination on defecation. Intensive Care Med. 2006 Jun;32(6):875-80. doi: 10.1007/s00134-006-0175-9. Epub 2006 Apr 28.

  PMID: 16715327 BACKGROUND

• Reintam Blaser A, Poeze M, Malbrain ML, Bjorck M, Oudemans-van Straaten HM, Starkopf J; Gastro-Intestinal Failure Trial Group. Gastrointestinal symptoms during the first week of intensive care are associated with poor outcome: a prospective multicentre study. Intensive Care Med. 2013 May;39(5):899-909. doi: 10.1007/s00134-013-2831-1. Epub 2013 Jan 31.

  PMID: 23370829 BACKGROUND

• Reintam A, Parm P, Kitus R, Starkopf J, Kern H. Gastrointestinal failure score in critically ill patients: a prospective observational study. Crit Care. 2008;12(4):R90. doi: 10.1186/cc6958. Epub 2008 Jul 14.

  PMID: 18625051 BACKGROUND

• Herndon CM, Jackson KC 2nd, Hallin PA. Management of opioid-induced gastrointestinal effects in patients receiving palliative care. Pharmacotherapy. 2002 Feb;22(2):240-50. doi: 10.1592/phco.22.3.240.33552.

  PMID: 11837561 BACKGROUND

• Masri Y, Abubaker J, Ahmed R. Prophylactic use of laxative for constipation in critically ill patients. Ann Thorac Med. 2010 Oct;5(4):228-31. doi: 10.4103/1817-1737.69113.

  PMID: 20981183 BACKGROUND

• Azevedo RP, Freitas FG, Ferreira EM, Machado FR. Intestinal constipation in intensive care units. Rev Bras Ter Intensiva. 2009 Aug;21(3):324-31. English, Portuguese.

  PMID: 25303556 BACKGROUND

• Sawh SB, Selvaraj IP, Danga A, Cotton AL, Moss J, Patel PB. Use of methylnaltrexone for the treatment of opioid-induced constipation in critical care patients. Mayo Clin Proc. 2012 Mar;87(3):255-9. doi: 10.1016/j.mayocp.2011.11.014.

  PMID: 22386181 BACKGROUND

• Hewitt K, Lin H, Faraklas I, Morris S, Cochran A, Saffle J. Use of methylnaltrexone to induce laxation in acutely injured patients with burns and necrotizing soft-tissue infections. J Burn Care Res. 2014 Mar-Apr;35(2):e106-11. doi: 10.1097/BCR.0b013e31829b399d.

  PMID: 23877147 BACKGROUND

Related Links

• Constipation in critically ill patients and its relationship to feeding and weaning from respiratory support

MeSH Terms

Conditions

Constipation; Critical Illness

Interventions

Polyethylene Glycols; polyethylene glycol 3350; naloxegol

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Ethylene Glycols; Glycols; Alcohols; Organic Chemicals; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Sadeq A. Quraishi, MD,MHA,MMSc

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: March 10, 2016
• Study Start: May 1, 2017
• Primary Completion: April 1, 2019
• Study Completion: December 1, 2019
• Last Updated: May 5, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)