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Trial record 49 of 171 for:    gastroenterology | Recruiting Studies | United States

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

This study is currently recruiting participants.
See Contacts and Locations
Verified November 2016 by Tufts Medical Center
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT02977286
First received: November 21, 2016
Last updated: November 30, 2016
Last verified: November 2016
  Purpose
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.

Condition Intervention Phase
Constipation Drug: Naloxegol Oral Tablet Drug: Placebo Oral Tablet Drug: Docusate Sodium 100 Mg oral capsule [Colace] Drug: Senna 217 Mg Oral Tablet Drug: Polyethylene Glycols Drug: Bisacodyl 10 mg Suppository Drug: Magnesium Citrate Oral Liquid Product Drug: Methylnaltrexone Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Time to first spontaneous bowel movement (SBM) administration [ Time Frame: First occurrence after study randomization during period of ICU admission or a maximum of 10 ICU days ]

Secondary Outcome Measures:
  • Time to first SBM [ Time Frame: First occurrence after initiation of IV opioid therapy during period of ICU admission or a maximum of 10 ICU days ]
  • ICU days without a SBM [ Time Frame: During period of ICU admission or a maximum of 10 ICU days ]
  • Occurrence of lower GI tract paralysis (≥3 days without a SBM) [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Average daily opioid requirement [in IV fentanyl equivalents (mcg)] [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily characterization of each SBM for size and consistency [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily characterization of use of the study laxative protocol [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Enteral nutrition administered/% of daily goal reached [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily fluid balance [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily maximal pain scale score [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily maximal Sedation Assessment Scale (SAS) score [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily presence of delirium using the Intensive Care Delirium Screening Checklist (ICDSC) [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Occurrence of lower GI tract paralysis requiring GI/surgical consultation [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Days without mechanical ventilation support and duration of ICU stay [ Time Frame: From ICU admission to ICU discharge or a maximum of 10 ICU days ]
  • Abdominal pressure measurement every 8 hours [ Time Frame: From randomization to ICU discharge (or removal of foley catheter) or a maximum of 10 ICU days ]
  • Daily presence of diarrhea (time from study drug initiation to first episode of diarrhea; days without a diaper or rectal tube) [ Time Frame: From randomization to ICU discharge or a maximum of 10 ICU days ]
  • Daily difference in the pre-dose and post-dose Clinical Opioid Withdrawal Scale (COWS) score (as evaluated by the bedside nurse before and 2 hours after the administration of the daily study drug dose) [ Time Frame: From randomization to discontinuation of study drug or a maximum 10 ICU days ]

Estimated Enrollment: 36
Study Start Date: November 2016
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Naloxegol Oral Tablet

Intervention: Naloxegol 25 mg (or 12.5 mg) tablet po (enteral) daily AND Docusate Sodium 100mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:

  1. Adverse event potentially attributable to the study drug.
  2. Use of Relistor.
  3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
  4. The participant has been administered 10 days of study medication.
  5. The participant is discharged from the ICU.
  6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.

Other Name: Movantik

Drug: Naloxegol Oral Tablet
Naloxegol Oral Tablet 25 mg (or 12.5 mg) po (enteral) daily
Other Name: Movantik
Drug: Docusate Sodium 100 Mg oral capsule [Colace]
Docusate Sodium 100 mg po (enteral) twice daily
Other Name: Colace
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.
Other Name: Senokot
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.
Other Name: Miralax
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.
Other Name: Dulcolax
Drug: Magnesium Citrate Oral Liquid Product
Administer one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation.
Other Name: Citromag
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.
Other Name: Relistor
Placebo Comparator: Placebo Oral Tablet

Intervention: Placebo tablet po (enteral) daily AND Docusate Sodium 100 mg Oral Capsule twice daily AND Study laxative protocol daily [that may include Senna 217 mg Oral Tablet, Polyethylene Glycols (Miralax), Magnesium Citrate Oral Liquid Product (Citromag), Bisacodyl 10 mg Suppository (Dulcolax) and Methylnaltrexone (Relistor)] until one of the following:

  1. Adverse event potentially attributable to the study drug.
  2. Use of Relistor.
  3. Scheduled opioid therapy is stopped for ≥ 24 hours and participant has ≥ 1 SBM since enrollment.
  4. The participant has been administered 10 days of study medication.
  5. The participant is discharged from the ICU.
  6. The participant requires the initiation of a strong CYP3A4 inhibitor medication.

Other Name: AstraZeneca provided Movantik placebo

Drug: Placebo Oral Tablet
Placebo Oral Tablet po (enteral) twice daily
Other Name: Official AstraZeneca placebo for Movantik
Drug: Docusate Sodium 100 Mg oral capsule [Colace]
Docusate Sodium 100 mg po (enteral) twice daily
Other Name: Colace
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.
Other Name: Senokot
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.
Other Name: Miralax
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.
Other Name: Dulcolax
Drug: Magnesium Citrate Oral Liquid Product
Administer one 10 oz bottle if no spontaneous bowel movement >/= 5 days after scheduled opioid initiation.
Other Name: Citromag
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.
Other Name: Relistor

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02977286

Contacts
Contact: John W Devlin, PharmD 617-636-6124 jdevlin@tuftsmedicalcenter.org

Locations
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: John W Devlin, PharmD    617-636-6124    jdevlin@tuftsmedicalcenter.org   
Contact: Erik Garpestad, MD    6176362362    egarpestad@tuftsmedicalcenter.org   
Sponsors and Collaborators
Tufts Medical Center
Investigators
Principal Investigator: Erik Garpestad, MD Tufts Medical Center
  More Information

Publications:
Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT02977286     History of Changes
Other Study ID Numbers: 11200
Study First Received: November 21, 2016
Last Updated: November 30, 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Constipation
Critical Illness
Paralysis
Signs and Symptoms, Digestive
Signs and Symptoms
Disease Attributes
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Analgesics, Opioid
Citric Acid
Bisacodyl
Magnesium citrate
Senna Extract
Sennoside A&B
Polyethylene glycol 3350
Bismuth subsalicylate
Methylnaltrexone
Naltrexone
Naloxegol
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anticoagulants
Calcium Chelating Agents
Chelating Agents
Sequestering Agents

ClinicalTrials.gov processed this record on July 21, 2017