Naloxegol for the Prevention of Constipation in Postoperative Spinal Surgery Patients

A Double-blind, Randomized, Placebo-controlled Trial of Naloxegol for Prevention of Post-operative Constipation in Spinal Surgery Patients

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.

Study Overview

• Status: Terminated
• Conditions: Constipation
• Intervention / Treatment: Drug: Sugar Pill; Drug: MOVANTIK™ (naloxegol)

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

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MOVANTIK™ (naloxegol); Subjects in the treatment group will be administered MOVANTIK™ (naloxegol) 25 mg tablet or placebo once daily beginning 2 hours after the completion of their surgery until their discharge from the hospital (variable timing). Subjects with renal impairments (creatine clearance rate of less than 60 mL/min) will receive a 12.5 mg dose tablet of naloxegol in place of the 25 mg dose as advised by FDA guidelines. For patients who are unable to swallow the tablet whole, the tablet can be crushed and given orally or administered via nasogastric tube.	Drug: MOVANTIK™ (naloxegol)
PLACEBO_COMPARATOR: Sugar pill; Matching placebo consists of an inert mixture supplied by AstraZeneca in identical-appearing tablets. Subjects in the placebo group will be administered a placebo tablet once daily beginning 2 hours after the completion of their surgery until their discharge from the hospital (variable timing).	Drug: Sugar Pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Post-operative Spontaneous Bowel Movement	The primary endpoint of the study was time to first post-operative bowel movement, as defined by the first spontaneous bowel movement reported by nursing staff after transfer from the surgical suite to the inpatient floor. A bowel movement was defined as the spontaneous passage of one tablespoon or more of liquid or solid stool (excluding flatus), which could be measured and verified by nursing staff. Time was measured in hours post-operatively with the starting time point marked at the end of the surgical procedure.	through study completion, an average of 6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Rescue Laxative Medication Use During Hospitalization	The use of a rescue laxative medication is defined as the administration of an additional bowel medication due to a decision by the clinical treatment team that the subject suffered from constipation and required a "rescue" bowel medication. Of note, this medication did not include the study drug, placebo, or the standing laxative orders used in all patient (docusate and sennosides). By definition, a rescue medication could only be given before a subject's first bowel movement or discharge	upon discharge from hospital, an average of 5 days
Length of Stay		through study completion, an average of 6 days
Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index	BFI normal reference range is 0-28.8 (on a scale of 100 for all 3 items summed and divided by 3). Higher scores mean a worse outcome.	through study completion, an average of 6 days
Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.	Patients completed a bowel satisfaction questionnaire on day of discharge. 5-point Likert scale, "Very dissatisfied" to "Very satisfied." Higher scores mean a better outcome.	upon discharge from hospital, an average of 5 days
Number of Participants That Experienced Diarrhea		through study completion, an average of 6 days

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (ACTUAL): February 1, 2018
• Study Completion (ACTUAL): February 1, 2018

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (ESTIMATE): October 27, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 20, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: 2016P001847; ESR-15-11338, D3820L00008 (OTHER_GRANT: AstraZeneca)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO