Clinical trial NCT02946580: Naloxegol for the Prevention of Constipation in Postoperative Spinal Surgery Patients
Official title: A Double-blind, Randomized, Placebo-controlled Trial of Naloxegol for Prevention of Post-operative Constipation in Spinal Surgery Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Constipation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2016-10-27
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Constipation is a known complication of the postoperative period after spinal surgery, where prescription pain medicines called opioids are traditionally used in high doses for the treatment of surgery-related pain. The goal of this study is to determine the effectiveness of Movantik (naloxegol)-a FDA-approved drug used to treat constipation that is caused by opioids-in preventing constipation in patients undergoing spinal fusion surgery at MGH.

Detailed description: We conducted a randomized, double-blind, placebo-controlled trial at a single, academic tertiary center (Massachusetts General Hospital, Boston, MA) from 2017 to 2018. Adult male and female patients between the ages of 18 and 80 who were planned to undergo non-urgent, elective posterior-approach spinal fusion surgeries by the Department of Neurosurgery were eligible for inclusion. Of note, patients with preexisting opioid and/or laxative use were still considered eligible and patients were not stratified according to these characteristics. Once a surgeon and the patient made a joint decision to proceed with elective, posterior spinal fusion surgery, patients would be approached by study personnel, with all eligible patients recruited independently of their surgeon to ensure no conflict of interest. After informed consent, eligible patients provided baseline demographic information including age, sex, race, pre-operative laxative use, and pre-operative opioid use. In addition, subjects completed a Bowel Function Index (BFI), a validated measure of opioid-induced constipation.10 Patients were not instructed to alter their daily regimen from time of consent to initiation of the study. On the day prior to scheduled surgery, clinical research pharmacy staff randomized subjects in a 1:1 ratio. With the exception of the pharmacist preparing the study drug or placebo, who was unaffiliated with the investigators or study sponsor, the individual treatment assignment was unknown to study staff, patients, sponsors, and clinical treatment teams.

Upon completion of surgery, post operative care unit nurses administered 25 mg of oral naloxegol (12.5 mg for creatinine clearance of \<60 mL/min) or an identical placebo within 2 hours of arrival in the recovery room post-operatively and then every 24 hours thereafter

Eligibility criteria: Inclusion Criteria:

* Male or female patients between the ages of 18 and 75 years undergoing non-urgent, elective spinal fusion at Massachusetts General Hospital who are admitted to the neurosurgery floor from the operating room

Exclusion Criteria:

* Patients who are taken to the operating room from another inpatient floor or service (already hospitalized prior to surgery)
* Patients with evidence of bowel obstruction
* Patients unable to take oral medications by mouth or by enteric feeding tube (gastrostomy or jejunostomy)
* Patients with a documented or potential allergy or adverse reaction to Movantik (naloxegol) from outpatient use
* Patients currently taking Movantik (naloxegol) in the outpatient setting
* Patients with a preoperative diagnosis of irritable bowel syndrome (IBS) obtained via Rome III questionnaire on screening
* Patients with disruptions to the blood-brain barrier (eg, multiple sclerosis, recent brain injury, Alzheimer's disease, and uncontrolled epilepsy)
* Patients with a history of cancer.
* Patients concomitantly using strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole), strong CYP3A4 inducers and other opioid antagonists.
* Patients with severe hepatic impairment.
* Patients with a previous history of or risk of bowel perforation.
* Patients with a post-op regional anesthetic technique employed like a continuous epidural or spinal.
* Patients for which local anesthetics will be placed in the wound.

Primary outcomes:
measure: Time to First Post-operative Spontaneous Bowel Movement
timeFrame: through study completion, an average of 6 days
Secondary outcomes:
measure: Time to Rescue Laxative Medication Use During Hospitalization
timeFrame: upon discharge from hospital, an average of 5 days
measure: Length of Stay
timeFrame: through study completion, an average of 6 days
measure: Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index
timeFrame: through study completion, an average of 6 days
measure: Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.
timeFrame: upon discharge from hospital, an average of 5 days
measure: Number of Participants That Experienced Diarrhea
timeFrame: through study completion, an average of 6 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Kyle Staller, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: