Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids
Condition: Constipation
MeSH terms: Paralysis; Constipation
Intervention: Naloxegol Oral Tablet; Placebo Oral Tablet; Docusate Sodium 100 Mg oral capsule [Colace]; Senna 217 Mg Oral Tablet; Polyethylene Glycols; Bisacodyl 10 mg Suppository; Magnesium Citrate Oral Liquid Product; Methylnaltrexone
Intervention description: Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily; Placebo Oral Tablet po (enteral) twice daily; Docusate Sodium 100 mg po (enteral) twice daily; Senna 127 mg oral tablet daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to two senna 127 mg tables if no no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=5 days after scheduled opioid initiation. Repeat two senna 127 mg tablets if no spontaneous bowel movement >/=6 days after scheduled opioid initiation.; Polyethylene Glycols 17 g daily if no spontaneous bowel movement >/=3 days after scheduled opioid initiation; increase to 34 g daily if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat 34 g daily if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.; Insert one suppository if no spontaneous bowel movement >/=4 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation. Repeat if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation.; Administer one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation.; Administer 8 mg or 16 mg (depending on subject's weight) subcutaneously x 1 if no spontaneous bowel movement >/= 6 days after scheduled opioid initiation, consult surgery/gastroenterology and discontinue study medication.
Intervention MeSH terms: Methylnaltrexone; Naloxegol; Bisacodyl; Magnesium citrate; Bismuth subsalicylate
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study evaluates the addition of naloxegol (Movantik) to a laxative protocol in
      critically ill adults requiring scheduled opioid (e.g. fentanyl) therapy. Half of the
      participants will receive naloxegol and a laxative protocol and half the participants will
      receive a placebo and a laxative protocol.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Admitted to an ICU

          -  Expected to require admission to an ICU for ≥ 48 hours

          -  Intravenous opioid administration in the prior 24 hours of ≥ 100 mcg fentanyl
             equivalents

        Exclusion Criteria:

          -  Scheduled use of an opioid ≥ 10 mg morphine equivalents per day in the week prior to
             ICU admission

          -  History of constipation (≤ 2 SBM per week and current use of stool softener or
             laxative therapy) prior to ICU admission

          -  Current scheduled use of a medication affecting gastric motility

          -  Current use of a medication known to be a strong CYP3A4 inhibitor

          -  History of a neurologic condition that may affect the permeability of the blood-brain
             barrier

          -  Acute GI condition (e.g., clinical evidence of acute fecal impaction/complete
             obstruction, acute surgical abdomen, acute GI bleeding)

          -  Condition affecting GI motility or function (e.g. inflammatory bowel disease requiring
             immunosuppressive therapy, symptomatic Clostridium difficile, active diverticular
             disease, surgery on the colon or abdomen within 60 days of ICU admission)

          -  Current use of total parenteral nutrition

          -  Administration of enteral nutrition through a jejunal tube

          -  Severe hepatic dysfunction

          -  Endstage renal disease defined as either i. calculated creatinine clearance ≤ 10ml/min
             or ii. Any current use of renal replacement therapy

          -  Inability to enroll in study and initiate study medication within 48 hours of the
             patient begin first initiated on scheduled IV opioid therapy after ICU admission

          -  Unreliable method for enteral, gastric and/or oral medication administration (e.g., no
             feeding tube, nasogastric tube is on suction)

          -  Current or previous use of an opioid antagonist agent (e.g., naloxegol,
             methylnaltrexone) in the past 30 days

          -  Pregnant or actively lactating females

          -  Current participation in another interventional clinical study

          -  Inability to obtain informed consent