Ancillary Effects of Oral Naloxegol (Movantik)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Ancillary Effects of Oral Naloxegol (Movantik)

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Naloxegol 25 MG
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Female or male aged at least 18 years American Society of Anesthesiologists physical status 1-4; Scheduled for elective primary hip or knee surgery under spinal anesthesia; Expected to receive intravenous patient-controlled analgesia (IV PCA) Expected to have significant postoperative pain Negative pregnancy test Exclusion Criteria: Severe hepatic impairment, with/or twice the upper normal levels of liver enzymes Severe renal impairment, or creatinine level > 2.0 History of bladder cancer Patients receiving perioperative regional anesthesia blocks Presence of a sacral nerve stimulator Medications (anticholinergic agents such as antihistamines, phenothiazines, antidepressants, antipsychotics), conditions or comorbidity causing urinary retention Patient with requirement of urinary catheter insertion before or immediately post-surgery due to immobility Urinary Tract Infections and other urogenital comorbidity (incontinence, cysto-ureteric reflux, known bladder retention) or conditions which can cause urinary retention Severe peptic ulcer disease, diverticular disease, infiltrative gastrointestinal tract malignancies, or peritoneal metastases 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 Gastrointestinal obstruction/Gastrointestinal perforation Strong CYP3A4 inhibitors (some antibiotics, antifungals, protease inhibitors, and antidepressants), Strong CYP3A4 inducers, Other opioid antagonists Hypersensitivity to MOVANTIK (naloxegol) or any of its excipients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Effect of Naloxegol on reversing opioid-related side effects in patients recovering from elective primary hip surgery under spinal anesthesia who will be randomly assigned to oral Naloxegol or placebo for two postoperative days or until the date of discharge, whichever occurs earlier. The design will be a randomized, double-blind, placebo-controlled trial of oral Naloxegol in adults having elective primary hip or knee surgery under spinal anesthesia. The study will be performed at the Cleveland Clinic hospitals.
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 |