Risk of Major Adverse Cardiovascular Events for Naldemedine and Other Medications for Opioid Induced Constipation in Adults With Chronic Non-Cancer Pain

Study Overview
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Brief Summary
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The research objective is to characterize the risk of a major adverse cardiovascular event (MACE) among new users of naldemedine versus new users of lubiprostone and new users of naloxegol as comparator opioid induced constipation (OIC) medications.

Official Title
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Risk of Major Adverse Cardiovascular Events Among Users of Naldemedine Compared With Other Medications Used for Opioid Induced Constipation in Adult Patients With Chronic Non-Cancer Pain in a Healthcare Claims Database

Conditions
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Opioid-induced Constipation

Intervention / Treatment
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* Drug: Naldemedine
* Drug: Lubiprostone
* Drug: Naloxegol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least one dispensing of naldemedine or lubiprostone or naloxegol without prior use in the database of either medication (index date) At least two dispensings of opioids within six months prior to and including the index date, with at least a combined 31 cumulative days supply At least 18 years of age or older on the index date At least six months of continuous health plan coverage that includes medical and pharmacy benefits prior to and including the index date Exclusion Criteria: Any acute MACE (non-fatal MI or non-fatal stroke) within six months before or on the index date Any cancer treatment or cancer pain diagnosis within six months before or on the index date Prior use of methylnaltrexone, alvimopan or naloxegol within six months before or on the index date

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Naldemedine<br>Patients with chronic non-cancer pain who initiated naldemedine treatment for opioid-induced constipation. | Drug: Naldemedine<br>* 0.2 mg tablet once a day at any time with or without food<br>* Other names: Symproic®;|
| Lubiprostone<br>Patients with chronic non-cancer pain who initiated lubiprostone treatment for opioid-induced constipation. | Drug: Lubiprostone<br>* 0.024 mg twice a day [adjust dose based on liver function]<br>* Other names: Amitiza®;|
| Naloxegol<br>Patients with chronic non-cancer pain who initiated naloxegol treatment for opioid-induced constipation. | Drug: Naloxegol<br>* 25 mg tablet once a day in morning, 1 hour before or 2 hours after food<br>* Other names: Movantik®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with a Major Adverse Cardiovascular Event | A composite of major adverse cardiovascular events, cardiovascular (CV) death, nonfatal myocardial infarction (MI), and non-fatal stroke. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Cardiovascular Death |  | 5 years | 
| Number of Participants with Nonfatal Myocardial Infarction |  | 5 years | 
| Number of Participants with Nonfatal Stroke |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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naloxegol, major adverse cardiovascular event (MACE), opioid induced constipation (OIC), lubiprostone, naldemedine