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

NCT ID: NCT02705378

Last Updated: 2021-05-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2017-05-31

Study Completion Date

2019-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Constipation Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Polyethylene glycol

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

Group Type ACTIVE_COMPARATOR

Polyethylene glycol

Intervention Type DRUG

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

naloxegol

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

Group Type EXPERIMENTAL

naloxegol

Intervention Type DRUG

Intervention would be given by OG or NG tube

Interventions

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Polyethylene glycol

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

Intervention Type DRUG

naloxegol

Intervention would be given by OG or NG tube

Intervention Type DRUG

Other Intervention Names

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Polyethylene glycol (PEG) miralax glycolax Movantik

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sadeq A. Quraishi, MD,MHA,MMSc

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

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Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 16803421 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14633751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17893628 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19592200 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20639749 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16715327 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23370829 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18625051 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11837561 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20981183 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25303556 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22386181 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23877147 (View on PubMed)

Related Links

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3642590/

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

Other Identifiers

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NaRC-ICU_temp

Identifier Type: -

Identifier Source: org_study_id

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