RELISTOR's Effects on Opioid-Induced Constipation

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

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.

Study Overview

• Status: Withdrawn
• Conditions: OIC
• Intervention / Treatment: Drug: Relistor Injectable Product; Drug: Docusate Calcium; Drug: Bisacodyl; Drug: Milk of magnesia; Drug: Magnesium citrate; Drug: Senna; Drug: Enema

Detailed Description

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75203
      • Methodist Moody Brain and Spine Institute, Methodist Dallas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with acute OIC in postoperative spinal surgery patients, specifically those undergoing 1-2 level anterior lumbar interbody fusion (ALIF) at Methodist Dallas Medical Center (MDMC)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Methodist Health System
• Investigators: Principal Investigator: Richard Meyrat, MD, Methodist Dallas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): April 22, 2022
• Study Completion (Actual): April 22, 2022

Study Registration Dates

• First Submitted: June 14, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Opioid-Induced Constipation; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Sensory System Agents; Gastrointestinal Agents; Narcotic Antagonists; Calcium-Regulating Hormones and Agents; Cathartics; Laxatives; Antacids; Antidiarrheals; Calcium; Bisacodyl; Magnesium Hydroxide; Magnesium Oxide; Bismuth subsalicylate; Methylnaltrexone; Magnesium citrate
• Other Study ID Numbers: 013.MBSI.2021.D

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No