Constipation Drug Induced
Conditions
Keywords
constipation, opioid
Brief summary
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
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.
Interventions
DRUGMethylnaltrexone Bromide 150 mg Oral Tablet
Methylnaltrexone Bromide 150 mg Oral Tablet
DRUGMethylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution [RELISTOR]_#1
Methylnaltrexone Bromide 12 MG Subcutaneous Solution
DRUGNaloxegol 25 MG Oral Tablet
Naloxegol 25 MG Oral Tablet
Sponsors
University of Missouri-Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Each participant will be receiving one injection and tablets which have been randomly assigned.
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Bowl Movement | 24 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Bowl Movement Within 24 Hours | 24 hours after administration of study drug | The secondary outcome of this study is the time to effectiveness of subcutaneous versus oral therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Methylnaltrexone Oral Tablets 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.
Methylnaltrexone Bromide 150 mg Oral Tablet: Methylnaltrexone Bromide 150 mg Oral Tablet | 4 |
| Methylnaltrexone Subcutaneous Injection 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.
Methylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution \[RELISTOR\]\_#1: Methylnaltrexone Bromide 12 MG Subcutaneous Solution | 3 |
| Naloxegol Oral Tablets 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.
Naloxegol 25 MG Oral Tablet: Naloxegol 25 MG Oral Tablet | 5 |
| Total | 12 |
Baseline characteristics
| Characteristic | Methylnaltrexone Oral Tablets | Naloxegol Oral Tablets | Methylnaltrexone Subcutaneous Injection | Total |
|---|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 28.3 | 62.8 years STANDARD_DEVIATION 18.8 | 55.3 years STANDARD_DEVIATION 16.5 | 57.8 years STANDARD_DEVIATION 20.4 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 3 Participants | 12 Participants |
| Region of Enrollment United States | 4 participants | 5 participants | 3 participants | 12 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 1 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 1 / 4 | 3 / 3 | 2 / 5 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 | 0 / 5 |
Outcome results
Primary
Occurrence of Bowl 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.
Time frame: 24 hours
Population: The number of participants who had a successful bowl movement within 24 hours of administration of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Methylnaltrexone Oral Tablets | Occurrence of Bowl Movement | 2 Participants |
| Methylnaltrexone Subcutaneous Injection | Occurrence of Bowl Movement | 2 Participants |
| Naloxegol Oral Tablets | Occurrence of Bowl Movement | 5 Participants |
Secondary
Time to Bowl Movement Within 24 Hours
The secondary outcome of this study is the time to effectiveness of subcutaneous versus oral therapy.
Time frame: 24 hours after administration of study drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Methylnaltrexone Oral Tablets | Time to Bowl Movement Within 24 Hours | 292.5 minutes | Standard Deviation 385.4 |
| Methylnaltrexone Subcutaneous Injection | Time to Bowl Movement Within 24 Hours | 256.5 minutes | Standard Deviation 21.9 |
| Naloxegol Oral Tablets | Time to Bowl Movement Within 24 Hours | 270.2 minutes | Standard Deviation 187.5 |