Clinical trial NCT03523520
Conditions: Constipation Drug Induced
Keywords: constipation opioid
Sponsor: University of Missouri-Columbia
Start date: 2020-12-23; Completion date: 2023-03-31
Enrollment: 15 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Methylnaltrexone Bromide 150 mg Oral Tablet intervention 2: Methylnaltrexone Bromide 12 MG/0.6 ML Subcutaneous Solution [RELISTOR]_#1 intervention 3: Naloxegol 25 MG Oral Tablet
Intervention descriptions: intervention 1: Methylnaltrexone Bromide 150 mg Oral Tablet intervention 2: Methylnaltrexone Bromide 12 MG Subcutaneous Solution intervention 3: Naloxegol 25 MG Oral Tablet

Protocol documents:
ICF_000.pdf: 























Prot_003.pdf: 
Project Proposal 
 
Methylnaltrexone versus Naloxegol | Kara B. 
Goddard 
MU Health 
EM Research Working Group 
Project Proposal 
 
Administrative Summary  
 
 
 
 
 
 
 
 
 
Project Title 
Methylnaltrexone versus Naloxegol in the Treatment of 
Opioid-Induced Constipation in the Emergency Department 
Primary Investigator  
Kara B. Goddard, PharmD, BCPS 
Others Involved 
Jeanise Butterfield, MD; Julie Stilley, PhD; Matthew 
Robinson, MD 
 
Estimated Budget 
 
Methylnaltrexone oral tablet - $17.07 per tablet 
Methylnaltrexone 12mg subcutaneous injection - $93.96 
Naloxegol 25mg oral tablet - $9.14 per tablet 
 
For 20 doses of each medication: 
$51.21x 20 = $1,024.20 
$93.96 x 20 = $1,879.20 
$9.14 x 20 = $182.80 
 
Total: $3,086.20 
 
Funding Source 
 
Missouri College of Emergency Physicians 
Protocol Version 
 
v2 
 
Protocol Date 
 
04/18/2023 
 
Special Considerations 
None 
 
 
 
Project Overview  
 
 
 
 
 
 
 
 
 
 
Background / Significance: 
Opioid-induced constipation can lead to serious complications, including small bowel 
obstruction, fecal impaction, and bowel perforation.1 Not only are the medical 
complications potentially severe, patient quality of life can also be impacted.2 Two 
agents are currently available for opioid-induced constipation – oral and subcutaneous 
methylnaltrexone and oral naloxegol.  Mechanistically, both agents antagonize the 


Project Proposal 
 
Methylnaltrexone versus Naloxegol | Kara B. 
Goddard 
peripheral mu-opioid receptor in the gastrointestinal tract to decrease constipation 
without reversing the systemic analgesic effects of opiates.3 The literature currently 
available has evaluated the effectiveness of each agent, not the comparative 
effectiveness of these agents. 
 
Purpose / Study Aims: 
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. 
Primary Outcome: 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 Outcomes: The secondary outcome of this study is the time to 
effectiveness of subcutaneous versus oral therapy. 
 
Feasibility (sample size, frequency of eligible patients, duration of study):  
Sample size: 15 patients (due to changes in standard of care procedures the 
enrollment goal had to be reduced) 
Duration: 2 years  
 
Study Procedure 
1.  
Methods 
a. Patients presenting to the Emergency Department with opioid 
induced constipation will be screened for inclusion in one of three 
groups: 
i. Methylnaltrexone oral tablets (total 450 mg)  
ii. Methylnaltrexone 12mg subcutaneous injection  
iii. Naloxegol oral tablets (total 25 mg)  
b. A pregnancy test will be administered to females of childbearing 
potential before administration of the study drug. 
c. After treatment patients will 
i. Have a successful bowel movement, thus completing their 
time in the study to continue with standard patient care 
ii. Not have a successful bowel movement after 3 hours, 
continue with standard patient care, and be contacted in 24 
hours to record the time of any successful bowel movements 
after the 3 hours study period 


Project Proposal 
 
Methylnaltrexone versus Naloxegol | Kara B. 
Goddard 
 
2. Data collected 
a. Age 
b. Sex 
c. Current medications 
d. History of constipation 
e. Time of last bowel movement 
f. Attempts to alleviate current constipation 
g. Time to successful bowel movement after treatment 
h. Phone number or other contact information 
i. Side effects noted by patient or staff 
 
3. Subjects 
a. Inclusion criteria 
i. Complaint of opioid-induced constipation refractory to other 
therapy (enemas, laxatives, stool softeners) 
ii. Age≥18y/o 
iii. Not pregnant or lactating (negative urinary pregnancy test) 
iv. No contraindication to Methylnaltrexone or Naloxegol 
b. Exclusion criteria 
i. Age<18y/o 
ii. Pregnancy or lactation 
iii. Contraindication to Methylnaltrexone or Naloxegol 
iv. Assigned NPO 
v. Small bowel obstruction 
 
4. Treatment of subjects 
a. If the subjects are eligible for inclusion they will be offered inclusion 
in the study by one of the Emergency Department faculty.  If they 
refuse participation they will be treated in a standard fashion.  
Patient follow-up will cease after 24 hours  
b. Benefits 
i. Patient benefits: patient may achieve relief from opioid-
induced constipation 
ii. Society benefits: To our knowledge, this is the first time 
these two drugs are being compared for their efficacy 
c. Risks: Allergic reaction, stomach/abdominal pain, gas, nausea, 
diarrhea, dizziness, increased sweating, hot flashes, flushing, 
tremor, chills, black or bloody stools, coughing up blood 
d. Compensation: The patients will not be compensated for study 
inclusion 
 
5. References 


Project Proposal 
 
Methylnaltrexone versus Naloxegol | Kara B. 
Goddard 
1. Jones R, Prommer E, Backstedt D. Naloxegol: A Novel Therapy in 
the Management of Opioid-Induced Constipation. Am J Hosp Palliat 
Care 2016;33(9):875-880. 
2. Anantharamu T, Sharma S, Gupta AK, et al.  Naloxegol: First oral 
peripherally acting mu opioid receptor antagonists for opioid-
induced constipation. J Pharmacol Pharmacother. 2015;6(3):188-
92.  
3. Bowers BL, Crannage AJ. The Evolving Role of Long-Term 
Pharmacotherapy for Opioid-Induced Constipation in Patients 
Being Treated for Noncancer Pain. J Pharm Pract. 2017 Jan 
1:897190017745395. doi: 10.1177/0897190017745395. [Epub 
ahead of print]. 
 

SAP_005.pdf: 
Study Title: Methylnaltrexone versus Naloxegol in the Treatment of Opioid-Induced 
Constipation in the Emergency Department 
NCT number: NCT03523520 
Date: 09/04/2024 
 
 
Statistical analysis plan 
Population: Patients with opioid-induced constipation refractory to other bowel regimens. 
Feasibility: (sample size, frequency of eligible patients, duration of study):   
Sample size: Sample size calculations were performed prior to study initiating resulting in the need 
for a total of 60 participants (14 in each arm [rounding up to 20 per arm], adding 18 participants to 
account for dropouts)  
Frequency predictions for feasibility: 5 patients per month   
Participants randomized in a 1:1:1 pattern assigned by pharmacy staff. Study investigators 
blinded to randomization and study drug.  
Statistical considerations: 
Previous statistical plan included frequency analyses by Chi-Square and parametric ANOVA 
calculations with pairwise comparisons.  
Due to local changing prescribing patterns of opioids, the potential participant population was 
reduced to levels of infeasibility for continuation of this study. Therefore, only descriptive statistics 
were performed. No conclusive tests were performed.