Ancillary Effects of Oral Naloxegol (Movantik)

The purpose of this study is to find out whether oral Naloxegol can reduce the side effects of opioid painkillers following surgery. This study aims to explore whether Naloxegol can similarly reduce opioid-induced side effects in post-surgical patients. About 130 surgery patients will participate in this study which is being conducted at Cleveland Clinic Main Campus.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Naloxegol 25 MG; Drug: Placebo

Detailed Description

Opioids are the gold standard for postoperative pain management, but they have been shown to produce uncomfortable side effects such as urinary retention (an inability to completely empty the bladder), constipation and nausea/vomiting. Clinical evidence demonstrates that Naloxegol can safely and effectively block these undesirable side effects while maintaining the painkilling effects of opioids in outpatients suffering from opioid-induced constipation.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female or male aged at least 18 years
3. American Society of Anesthesiologists physical status 1-4;
4. Scheduled for elective primary hip or knee surgery under spinal anesthesia;
5. Expected to receive intravenous patient-controlled analgesia (IV PCA)
6. Expected to have significant postoperative pain
7. Negative pregnancy test

Exclusion Criteria:

1. Severe hepatic impairment, with/or twice the upper normal levels of liver enzymes
2. Severe renal impairment, or creatinine level > 2.0
3. History of bladder cancer
4. Patients receiving perioperative regional anesthesia blocks
5. Presence of a sacral nerve stimulator
6. Medications (anticholinergic agents such as antihistamines, phenothiazines, antidepressants, antipsychotics), conditions or comorbidity causing urinary retention
7. Patient with requirement of urinary catheter insertion before or immediately post-surgery due to immobility
8. Urinary Tract Infections and other urogenital comorbidity (incontinence, cysto-ureteric reflux, known bladder retention) or conditions which can cause urinary retention
9. Severe peptic ulcer disease, diverticular disease, infiltrative gastrointestinal tract malignancies, or peritoneal metastases
10. Patients with known or suspected disruption of blood brain barrier, which may include but not limited to: Alzheimer's disease, stroke, poliomyelitis, cerebral palsy, multiple sclerosis, spinal lesions, and Parkinson's disease
11. Gastrointestinal obstruction/Gastrointestinal perforation
12. Strong CYP3A4 inhibitors (some antibiotics, antifungals, protease inhibitors, and antidepressants), Strong CYP3A4 inducers, Other opioid antagonists
13. Hypersensitivity to MOVANTIK (naloxegol) or any of its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Naloxegol 25 mg given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first	Drug: Naloxegol 25 MG; Oral Naloxegol 25 MG; Other Names: Movantik
Placebo Comparator: Placebo Arm; Matching placebo given once in the morning every day until Post-operative Day 3 or day of discharge whichever occurs first	Drug: Placebo; matching oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Urine Volume	Residual urine volume in the bladder as assessed by bladder scan	from Postoperative days 1 to POD 2 or until day of discharge whichever occurs first

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side Effects of Naloxegol on Other Opioid Related Side Effects	Opioid-related Symptom Distress Scale (ORSDS) is a 4 point-scale that evaluates three symptom distress dimensions (frequency, severity, bothersomeness) for opioid-related side effects. The 12 elements of the ORSDS are nausea, vomiting, constipation, difficulty passing urine, difficulty concentrating, drowsiness, lightheaded, fatigue, feeling confused, itchiness, dry mouth, and headache. The ORSDS questionnaire was administered by a trained investigator on first and second postoperative days while patients remained hospitalized. We reported the average ORSDS score from all 12 elements, which ranged from 0 to 4 and higher scores represent worse outcome.	Postoperative days 1-2 or until day of discharge whichever occurs first
Need for Indwelling Urinary Catheterization	Number of patients receiving Naloxegol requiring indwelling urinary catheters	Postoperative days 1-2 or until day of discharge whichever occurs first
Quality of Recovery	Quality of recovery is a validated scoring system that quantifies patients' early postoperative health status with range of 0-150 where higher score means better quality of recovery. We used the 15-question version, the QoR-15	Postoperative Days 2 or discharge day whichever was earlier

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Investigators: Principal Investigator: Mehmet A Turan, MD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 28, 2017
• First Posted (Actual): August 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxegol
• Other Study ID Numbers: 17-765

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data to be provided in aggregate without patient identifiers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No