Ancillary Effects of Oral Naloxegol (Movantik)

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.

• Naloxegol 25 MG (Drug), also known as Movantik: Oral Naloxegol 25 MG
• Placebo (Drug): matching oral placebo

Primary outcomes

• Residual Urine Volume [from Postoperative days 1 to POD 2 or until day of discharge whichever occurs first]: Residual urine volume in the bladder as assessed by bladder scan

Secondary outcomes

• Side Effects of Naloxegol on Other Opioid Related Side Effects [Postoperative days 1-2 or until day of discharge whichever occurs first]: 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.
• Need for Indwelling Urinary Catheterization [Postoperative days 1-2 or until day of discharge whichever occurs first]: Number of patients receiving Naloxegol requiring indwelling urinary catheters
• Quality of Recovery [Postoperative Days 2 or discharge day whichever was earlier]: 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

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• Residual Urine Volume (Primary), Median, ml: Treatment-Naloxegol 62 (5 to 187); Placebo Arm 114 (13 to 247) (p 0.84)
• Side Effects of Naloxegol on Other Opioid Related Side Effects (Secondary), Median, log(score on a scale): Treatment-Naloxegol 0.53 (0.34 to 0.79); Placebo Arm 0.45 (0.31 to 0.81) (p 0.91)
• Need for Indwelling Urinary Catheterization (Secondary), Count of participants, Participants: Treatment-Naloxegol 19; Placebo Arm 7 (p 0.012)
• Quality of Recovery (Secondary), Median, units on a scale: Treatment-Naloxegol 119 (103 to 131); Placebo Arm 123 (115 to 133) (p 0.08)

Adverse events

Time frame: until discharge from hospital, an average of 2 day, up to 3 days

Serious adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2019-11-26)
• Informed Consent Form (PDF, 2017-05-23)

• Mehmet A Turan, MD, Principal investigator, The Cleveland Clinic