Methylnaltrexone vs Naloxegol in the Treatment of Opioid-Induced Constipation

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of subcutaneous versus oral mu-opioid receptor antagonist therapy in opioid induced constipation that is refractory to other bowel regimens.

Detailed Description
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Opioid-induced constipation can lead to serious complications, including small bowel obstruction, fecal impaction, and bowel perforation. Not only are the medical complications potentially severe, patient quality of life can also be impacted. Two agents are currently available for opioid-induced constipation - oral and subcutaneous methylnaltrexone and oral naloxegol. Mechanistically, both agents antagonize the peripheral mu-opioid receptor in the gastrointestinal tract to decrease constipation without reversing the systemic analgesic effects of opiates. The literature currently available has evaluated the effectiveness of each agent, not the comparative effectiveness of these agents.

Official Title
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Methylnaltrexone Versus Naloxegol in the Treatment of Opioid-Induced Constipation in the Emergency Department

Conditions
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Constipation Drug Induced

Intervention / Treatment
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* Drug: Methylnaltrexone Bromide 150 mg Oral Tablet
* Drug: Methylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution [RELISTOR]_#1
* Drug: Naloxegol 25 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Complaint of opioid-induced constipation refractory to other therapy (enemas, laxatives, stool softeners) Age≥18y/o Not pregnant or lactating (negative urinary pregnancy test) No contraindication to Methylnaltrexone or Naloxegol Exclusion Criteria: Age<18y/o Pregnancy or lactation Contraindication to Methylnaltrexone or Naloxegol Assigned NPO Small bowel obstruction

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: Participants will be assigned to one of three groups i. Methylnaltrexone oral tablets (total 450 mg) + subcutaneous water injection ii. Methylnaltrexone 12mg subcutaneous injection + placebo sugar tablets iii. Naloxegol oral tablets (total 25 mg) + subcutaneous water injection
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylnaltrexone oral tablets<br>Methylnaltrexone oral tablets (total 450 mg) + subcutaneous water injection Eligible patients with complaint of opioid-induced constipation will receive this treatment after study enrollment. Time to bowel movement will be recorded until 3 hours in the emergency department, and patient will be contacted after 24 hours if bowel movement was not achieved after the 3 hours. | Drug: Methylnaltrexone Bromide 150 mg Oral Tablet<br>* Methylnaltrexone Bromide 150 mg Oral Tablet<br>* Other names: Relistor;|
| Active Comparator: Methylnaltrexone subcutaneous injection<br>Methylnaltrexone 12mg subcutaneous injection + sugar placebo tablet Eligible patients with complaint of opioid-induced constipation will receive this treatment after study enrollment. Time to bowel movement will be recorded until 3 hours in the emergency department, and patient will be contacted after 24 hours if bowel movement was not achieved after the 3 hours. | Drug: Methylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution [RELISTOR]_#1<br>* Methylnaltrexone Bromide 12 MG Subcutaneous Solution<br>* Other names: Relistor;|
| Active Comparator: Naloxegol oral tablets<br>Naloxegol oral tablets (total 25 mg) + subcutaneous water injection Eligible patients with complaint of opioid-induced constipation will receive this treatment after study enrollment. Time to bowel movement will be recorded until 3 hours in the emergency department, and patient will be contacted after 24 hours if bowel movement was not achieved after the 3 hours. | Drug: Naloxegol 25 MG Oral Tablet<br>* Naloxegol 25 MG Oral Tablet<br>* Other names: Movantik;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Bowel Movement | The primary outcome of this study is to determine the effectiveness of peripherally acting mu-opioid receptor antagonist therapy for patients presenting to the emergency department (ED) with opioid-induced constipation. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subcutaneous vs Oral | The secondary outcome of this study is the time to effectiveness of subcutaneous versus oral therapy. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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constipation, opioid