RELISTOR's Effects on Opioid-Induced Constipation

Study Overview
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Brief Summary
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This will be a prospective case-control study of 40 patients undergoing 1-2 level ALIF procedures at Methodist Dallas Medical Center (MDMC). Patient records will be reviewed to identify details including demographics, comorbidities, procedure details, and the primary and secondary outcome metrics.

Detailed Description
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RELISTOR is a legally marketed device and will be used off-label under the authority of a health care practitioner within a legitimate practitioner-patient relationship with the intent of the practice of medicine. The use of RELISTOR in the experimental group of this study meets all of the following conditions: is not intended to be reported to the FDA in support of a new indication for use or to support any other significant change in the labeling for the drug; it is not intended to support a significant change in the advertising for the product; it does not involve a route of administration or dosage level, use in a subject population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product; it is conducted in compliance with the requirements for IRB review and informed consent [21 CFR parts 56 and 50, respectively]; it is conducted in compliance with the requirements concerning the promotion and sale of drugs [21 CFR 312.7]; and it does not intend to invoke 21 CFR 50.24 Screening and Enrollment: Patients will undergo two levels of screening: the initial screening and a post-operative OIC screening. The initial screening will involve all 1-2 level ALIF patients in the experimental group and observational group who will be approached to participate in the study before surgery. After eligible patients agree to participate and sign the ICF, all patients will then be asked to complete the PAC-SYM instrument about their constipation symptoms over the past 2 weeks. Patients in both groups will undergo their 1-2 level ALIF procedure and then will undergo the post-operative OIC screen/rescreen (as needed) daily for acute OIC for a maximum of 3 days (i.e., postoperative days 2 - 4). Patients who are found to have acute OIC will be designated to the experimental and observational treatment regimens accordingly to Study Treatment Regimens. If a patient does not have acute OIC after they are rescreened on postoperative day 4, are discharged, or do not meet the inclusion criteria, will be placed in the not-constipated or post-operative screen failure group.

Official Title
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RELISTOR's Effects on Opioid-Induced Constipation in Postoperative 1-2 Level Anterior Lumbar Interbody Fusion Patients: A Case-Control Study

Conditions
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OIC

Intervention / Treatment
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* Drug: Relistor Injectable Product
* Drug: Docusate Calcium
* Drug: Bisacodyl
* Drug: Milk of magnesia
* Drug: Magnesium citrate
* Drug: Senna
* Drug: Enema


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Experimental Group (initial screen): Age 18 years or older Inpatient who will undergo a 1-2 level ALIF procedure with Dr. Richard Meyrat Are not pregnant or lactating Does not have a history of drug abuse within the past 2 years Does not have a gastrointestinal ostomy Experimental Group (post-operative OIC screen/rescreen) Actively constipated (i.e., no BM in last 48 hours, difficult having a spontaneous BM, or inability to have a spontaneous BM) Receiving mu-agonist opioids Expected to require daily opioid analgesics for at least 7 days following enrollment Have not received or discontinued use of any laxatives, enemas and/or promotility agents within 48 hours of enrollment and the first dose of RELISTOR. Stool softeners are permitted. Does not have a known hypersensitivity to methylnaltrexone, naltrexone, or naloxone Observational Group (initial screen): Age 18 years or older Inpatient who will undergo 1-2 level ALIF procedure with Dr. Graham Are not pregnant or lactating Does not have a history of drug abuse within the past 2 years Does not have a gastrointestinal ostomy Observational Group (post-operative OIC screen/rescreen): Actively constipated (i.e. no BM in last 48 hours, difficulty having a spontaneous BM, or inability to have a spontaneous BM) Receiving mu-agonist opioids Expected to require daily opioid analgesics for at least 7 days following enrollment Exclusion Criteria: Experimental Group (post-operative OIC screen/rescreen): Exclude patients with: Fecal impaction Mechanical bowel obstruction Constipation not attributed to post-procedural opioid use Calculated creatinine clearance less than 50 mL/min Corrected QT interval greater than 500 msec. on a 12-lead screening electrocardiogram Observational Group (post-operative OIC screen/rescreen): Exclude patients with: Fecal impaction Mechanical bowel obstruction Constipation not attributed to post-procedural opioid use

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 |
| --- | --- |
| Experimental Group<br>Patients who receive RELISTOR | Drug: Relistor Injectable Product<br>* 12-mg RELISTOR to be administered as once-daily subcutaneous injections for 4 to 7 days<br>|
| Observational Group<br>Patients that receive standard of care | Drug: Docusate Calcium<br>* Standard of care<br>Drug: Bisacodyl<br>* Standard of Care<br>Drug: Milk of magnesia<br>* Standard of Care<br>Drug: Magnesium citrate<br>* Standard of Care<br>Drug: Senna<br>* Standard of Care<br>Drug: Enema<br>* Standard of Care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel Movement assessment | Percentage of patients with bowel movement (BM) within four hours of first RELISTOR dose or SOC bowel regimen | July 2021 - April 2022 | 
| Post-treatment Bowel Movement | Time to Bowel Movement after first treatment | July 2021 - April 2022 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Assessment of Constipation Symptoms (PAC-SYM) | to measure patient's self-reported experience of symptoms and symptom severity in constipation pre-operatively and at patients post-operative follow-up | July 2021 - April 2022 | 
| Treatment Satisfaction Questionnaire for Medication | to measure patients' satisfaction with medication | July 2021 - April 2022 | 
| Bowel Function Diary | Daily Assessment Module: to measure constipation symptoms experienced in the past 24 hours during hospitalization | July 2021 - April 2022 |