Constipation, Critical Illness
Conditions
Keywords
Intensive care unit, ICU, Critical Illness, Constipation
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.
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.
Interventions
DRUGPolyethylene glycol
Intervention would be given by oro-gastric (OG) or naso-gastric (NG) tube
DRUGnaloxegol
Intervention would be given by OG or NG tube
Sponsors
AstraZeneca
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Laxation within 48 hours of starting second-line agent | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to first bowel movement after starting second-line agent | 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 |
| Doses of second-line laxative agent before bowel movement | 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 |
| Protein/caloric deficit | 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 |
| Feeding interruptions | 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 |
Countries
United States
Outcome results
None listed