NCT02977286

Naloxegol to Prevent Lower Gastrointestinal Paralysis in Critically Ill Adults Administered Opioids

Impact of Naloxegol on Prevention of Lower GI Tract Paralysis in Critically Ill Adults Initiated on Scheduled Intravenous Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Tufts Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Among the more than 5 million adults who are admitted to the ICU each year in the USA, most have pain and thus receive a pain (analgesic) medication called an opioid. Opioid use in critically ill adults continues to increase given the greater awareness of untreated pain in the ICU and that an opioid-first approach be used to optimize patient safety and comfort and improve tolerance with breathing machines (i.e. mechanical ventilation). Similar to constipation, paralysis of the lower gastrointestinal (GI) tract is defined as the inability to pass stool due to impaired gut movement, and is a common effect of opioid use in the critically ill. Lower GI tract paralysis may lead to nausea, vomiting, aspiration, compromise the ability to administer tube feeds (enteral nutrition), an increase abdominal pain, delirium and delay getting off mechanical ventilation. One recent randomized study found that aggressive use of laxatives to prevent lower GI tract paralysis in critically ill adults was associated with lower daily organ dysfunction \[as measured by the Sequential Organ Failure Assessment (SOFA) score\]. The lower GI tract paralysis that occurs in the critically ill often responds poorly to laxative medication therapy (e.g., senna, bisacodyl, lactulose). While stool softener medications like docusate are routinely administered to patients on opioids, laxative-based protocols are frequently not initiated in the ICU until signs of lower GI tract paralysis start to appear. There is therefore an important and unmet need for a safe and efficacious medication to prevent lower GI tract paralysis in critically ill adults who are initiated on opioid therapy. Naloxegol (Movantik) is a naloxone-like drug that blocks the effect of opioids on the opioid µ receptor in the gut but is not absorbed in the brain (and therefore does not block the pain effects of opioids). Naloxegol is currently approved by the Food and Drug Administration (FDA) for the treatment of opioid-induced constipation (OIC) in non-ICU patients receiving scheduled moderate to high dose opioids for the treatment of chronic non-cancer pain. Naloxegol has a mechanism of action, efficacy, convenience of administration, and safety profile that make it an ideal candidate for use as a preventative medication for lower GI tract paralysis in critically ill adults receiving scheduled opioid therapy. The investigators propose a pilot study in which they will test the hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous bowel movement (SBM) that an ICU patient has, that it will prevent lower GI tract paralysis in critically ill adults initiated on scheduled IV opioid therapy, and its use will not result in side effects that are concerning to doctors or patients. The investigators will randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol \[25mg or 12.5mg (in patients with a creatinine clearance ≤ 60ml/min)\] or placebo. This pilot study will provide valuable information to help guide future, larger studies evaluating the role of naloxegol in critically ill adults.

Conditions

• Constipation

Interventions

Type	Name	Description
DRUG	Naloxegol Oral Tablet	Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily
DRUG	Placebo Oral Tablet	Placebo Oral Tablet po (enteral) twice daily
DRUG	Docusate Sodium 100 Mg oral capsule [Colace]	Docusate Sodium 100 mg po (enteral) twice daily
DRUG	Senna 217 Mg Oral Tablet	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.
DRUG	Polyethylene Glycols	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.
DRUG	Bisacodyl 10 mg Suppository	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.
DRUG	Magnesium Citrate Oral Liquid Product	Administer one 10 oz bottle if no spontaneous bowel movement \>/= 5 days after scheduled opioid initiation.
DRUG	Methylnaltrexone	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.

Timeline

• Start date: 2017-01-01
• Primary completion: 2019-10-09
• Completion: 2019-10-09
• First posted: 2016-11-30
• Last updated: 2023-02-16
• Results posted: 2023-02-16

Locations

1 site across 1 country: United States