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Naloxegol for Prevention of Lower GI Tract Paralysis in Critically Ill Adults


Title Impact of Naloxegol (Movantik) on Prevention of Lower Gastrointestinal Tract Paralysis in Critically Ill Adults Initiated on Scheduled IV Opioid Therapy: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Single-Center, Proof of Concept Study
Therapeutic Area Constipation, Lower GI Tract Paralysis
Principal Investigator Erik Garpestad, MD
Min Age 18 Years
Gender All
Contact John Devlin, Pharm D
617-636-6124
More Information https://clinicaltrials.gov/ct2/show/NCT02977286

Overview

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 population and a recent strong recommendation in the Society of Critical Care Medicine’s Pain, Agitation, and Delirium Guidelines for Critically Ill Adults 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 movements, and is a common effect of opioid use in the critically ill. Lower GI tract paralysis will often lead to nausea, vomiting, aspiration, compromise the ability to administer tube feeds (enteral nutrition), increases abdominal pain, and has been shown to 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 docusateare 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. 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 opioid therapy through the vein [intravenous (IV)]. We therefore propose a pilot study in which we will test the hypothesis that naloxegol (versus placebo) will reduce the time to the first spontaneous bowel movement (SBM) that the 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. We will randomize 36 critically ill ICU patients (18 in each arm) to receive naloxegol [25mg or 12.5mg (in patients with kidney problems] or placebo. This pilot study will provide valuable information to help guide future, larger studies of naloxegol in ICU patients.

Study Details

Inclusion Criteria

  • Admitted to the Medical ICU service at Tufts Medical Center
  • Administered ≥ 100 mcg IV fentanyl (or equivalent) in the past 24 hours

Exclusion Criteria

  • Scheduled use of opioids (≥ 10mg morphine equivalents per day) prior to ICU admission
  • History of constipation as defined by schedules use of bisacodyl, senokot, lactulose and/or PEG 3350 (Miralax)
  • Acute GI condition (e.g., fecal imaction, gastric obstruction, acute surgical abdomen, acute GI bleeding).

Study Requirements

All research activities will occur while the patient is admitted to the Medical ICU service at Tufts Medical Center. No blood draws will be taken as part of this study. Most study data is collected by the bedside nurse (e.g., number and consistency of stools) and bladder pressures (for patients who have a urinary catheter in place for clinical reasons)