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

Constipation Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Constipation
• Paralysis

• NCT number: NCT02977286
• Study type: Interventional
• Source: Tufts Medical Center
• Status: Terminated
• Phase: Phase 4
• Start date: January 1, 2017
• Completion date: October 9, 2019