ConstipationPhase 3NaRC-ICUNCT02705378
The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit
A Phase 3 study testing Polyethylene glycol and naloxegol in people with Constipation and Critical Illness, run by Massachusetts General Hospital at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Constipation, Critical Illness
- What is being tested?
- Polyethylene glycol and naloxegol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- May 2017to Dec 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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.
Read the 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.
- Conditions
- Constipation, Critical Illness
- Being tested
- Polyethylene glycol, naloxegol
- Keywords
- Intensive care unit, ICU, Critical Illness, Constipation
- Medical subject headings
- Constipation, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Polyethylene glycolDrug
Also called Polyethylene glycol (PEG), miralax, glycolax
Intervention would be given by oro-gastric (OG) or naso-gastric (NG) tube
naloxegolDrug
Also called Movantik
Intervention would be given by OG or NG tube
| Study group | Role | What they receive |
|---|---|---|
| Polyethylene glycol | Active comparator | 17g power qday; reconstituted in water for naso/orogastric tube administration Receives: Drug: Polyethylene glycol |
| naloxegol | Experimental | 25mg qday; crushed pill reconstituted in water for naso/orogastric tube administration Receives: Drug: naloxegol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Number of hours from initiation of a second-line laxative agent until first documented bowel movement
Measured: From 72 hours after ICU admission until 120 hours after ICU admission
Doses of second-line laxative agent before bowel movement
Number of doses of second-line laxative agent until first documented bowel movement
Measured: From 72 hours after ICU admission until 120 hours after ICU admission
Protein/caloric deficit
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
Measured: From admission to the ICU until the end of day 7 after ICU admission
Feeding interruptions
Number of interruptions to enteral nutrition for high gastric residual volume during study period
Measured: From admission to the ICU until the end of day 7 after ICU admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study startMay 2017 (estimated)
- Primary completionApr 2019 (estimated)
- Study completionDec 2019 (estimated)
Why it stopped: PI left institution. Protocol never submitted to the IRB, no contract executed only Confidentiality Agreement, and study not done.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for ConstipationStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Sadeq A. Quraishi, MD,MHA,MMSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02705378
- Sponsor's protocol ID
- NaRC-ICU_temp
- Acronym
- NaRC-ICU
- Status last verified
- Apr 2021
- First submitted
- 5 Feb 2016
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 16803421Mostafa 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.
PubMed 14633751van 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.
PubMed 17893628Nassar 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.
PubMed 19592200Gacouin 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.
PubMed 20639749van 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.
PubMed 16715327Reintam 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.
PubMed 23370829Reintam 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.
PubMed 18625051Herndon 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.
PubMed 11837561Masri 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.
PubMed 20981183Azevedo 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.
PubMed 25303556Sawh 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.
PubMed 22386181Hewitt 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.
PubMed 23877147
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Naloxegol on Refractory Constipation in the Intensive Care Unit
- ClinicalTrials.gov ID
- NCT02705378
- Acronym / sponsor ID
- NaRC-ICU / NaRC-ICU_temp
- Conditions
- Constipation, Critical Illness
- Keywords
- Intensive care unit, ICU, Critical Illness, Constipation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI left institution. Protocol never submitted to the IRB, no contract executed only Confidentiality Agreement, and study not done.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- May 2017 (estimated)
- Primary completion
- Apr 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 10 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Polyethylene glycol | Active comparator | Drug: Polyethylene glycol17g power qday; reconstituted in water for naso/orogastric tube administration |
| naloxegol | Experimental | Drug: naloxegol25mg qday; crushed pill reconstituted in water for naso/orogastric tube administration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Polyethylene glycolAlso: Polyethylene glycol (PEG), miralax, glycolaxIntervention would be given by oro-gastric (OG) or naso-gastric (NG) tube | Drug | Polyethylene glycol |
| naloxegolAlso: MovantikIntervention would be given by OG or NG tube | Drug | naloxegol |
Primary outcome
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
4 secondary outcomes
Time to first bowel movement after starting second-line agent
Time frame: 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
Protein/caloric deficit
Time frame: 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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Background: PubMed 16803421Patanwala 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.
- Background: PubMed 14633751Mostafa 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.
- Background: PubMed 17893628van 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.
- Background: PubMed 19592200Nassar 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.
- Background: PubMed 20639749Gacouin 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.
- Background: PubMed 16715327van 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.
- Background: PubMed 23370829Reintam 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.
- Background: PubMed 18625051Reintam 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.
- Background: PubMed 11837561Herndon 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.
- Background: PubMed 20981183Masri 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.
- Background: PubMed 25303556Azevedo 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.
- Background: PubMed 22386181Sawh 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.
- Constipation in critically ill patients and its relationship to feeding and weaning from respiratory supportLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sadeq A. Quraishi, MD,MHA,MMSc principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Polyethylene glycol and naloxegol in people with Constipation and Critical Illness, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Laxation within 48 hours of starting second-line agent (time frame: From 72 hours after ICU admission until 120 hours after ICU admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02705378, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2021.