Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery

Phase 2

Recruiting

• Conditions: Postoperative Ileus
• Interventions: Other: Placebo; Drug: Pyridostigmine Bromide

• Registration Number: NCT05334485
• Lead Sponsor: Stefan Holubar MD MS FACS, FASCRS

Brief Summary

A double blind, placebo controlled, randomized control trial studying the safety and efficacy of pyridostigmine as a rescue therapy for postoperative ileus. Patients who undergo elective colorectal resection with or without creation of an ostomy, and subsequently develop postoperative ileus will be eligible for enrollment. Patients will be randomized to receive either pyridostigmine or placebo in addition to the current elements of standard of care. Patients will also complete the pyridostigmine bromide side effects scale (PBSES) upon enrollment and following each administration of either intervention or placebo to monitor treatment safety and evaluate for the development of side effects.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-09
• Study First Submitted QC: 2022-04-12
• Study First Posted: 2022-04-19
• Study Start: 2024-09-03
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-11
• Last Update Posted: 2024-11-12
• Primary Completion: 2025-09
• Study Completion: 2025-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Adult (age 18 and over) patients with benign or malignant colonic or rectal disease who have undergone elective laparoscopic, robotic, or open colorectal resections with or without ostomy construction at our center, and subsequently developed POI, defined as symptoms of bloating with or without nausea and vomiting, with absence of passage of flatus or stool for at least 48 hours postoperatively and require return to NPO status after initial diet attempts with or without placement of an NGT.

2. Radiographic confirmation of POI diagnosis either via abdominal radiography (KUB), computed tomography abdomen/pelvis (CT A/P), or both

3. ECOG Performance status < 4

4. Laboratory evidence of normal organ function, defined as:

   1. Hemoglobin ≥ 7.0 g/dL
   2. WBC ≤ 20,000/mcL and ≥ 4,000/mcL
   3. Platelet count ≥ 100,000/mcL or ≤ 100,000,000/mcL
   4. AST (SGOT) ≤ 2.5 times the institutional upper limit of normal
   5. ALT (SGPT) ≤ 2.5 times the institutional upper limit of normal
   6. Total bilirubin within the upper limit of institutional normal range
   7. Serum Creatinine within the upper limit of institutional normal range

Exclusion Criteria

1. Radiographic evidence of bowel obstruction
2. Documented intraabdominal septic complications (IASC, such as abdominopelvic abscess, peritonitis, anastomotic leak) at any time prior to or after enrollment
3. Isolated small bowel or ostomy surgery without colon or rectal resection
4. ASA score 5
5. Pregnant or breastfeeding females as PYR is classified by the FDA as a pregnancy risk category C medication with the potential for teratogenic or abortifacient effects and demonstrated secretion into breastmilk with an unknown but potential risk for adverse effects in the nursing infants
6. Current use of any other investigational agents including: neostigmine or other acetylcholine esterase inhibitors, alvimopan, metoclopramide, erythromycin, methylnaltrexone, naloxegol, cisapride, and laxatives or cathartics (i.e. milk of magnesia, polyethylene glycol)
7. History of allergic reactions attributed to PYR or other acetylcholine esterase inhibitors
8. Patients with any of the following uncontrolled, concurrent illnesses: active or latent MG, bronco-constrictive disease (asthma/reactive airway disease), chronic obstructive lung disease (COPD), symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia including bradycardia, renal failure, hepatic failure, gastroparesis, short bowel syndrome (small bowel < 200cm), preexisting short or large bowel dysmotility or pseudo-obstruction, chronic constipation/laxative use, peritoneal carcinomatosis, and psychiatric illness/social situations that would limit compliance with study requirements

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients randomized to this group will be given starch orally, every 12 hours for a maximum of 48 hours.
Pyridostigmine	Pyridostigmine Bromide	Patients randomized to this group will be given 60mg of pyridostigmine bromide orally, every 12 hours. Pyridostigmine will be administered from the time of diagnosis of postoperative ileus until the return of bowel function, or for a maximum of 48 hours.

Primary Outcome Measures

Name	Time	Method
Time until return of bowel function	Time from administration of pyridostigmine bromide or placebo until first passage of flatus for up to 30 days	Following the administration of either pyridostigmine bromide or placebo, the time (in minutes) until return of bowel function will be recorded. Return of bowel function is defined as the first passage of flatus.
Incidence of pyridostigmine bromide associated side effects	Participants will complete the survey at enrollment and then again at 30 minutes following each administration of either pyridostigmine bromide or placebo.	Side effects of pyridostigmine bromide will be assessed using the Pyridostigmine Bromide Side Effects Scale (PBSES) survey tool. Participants will complete this survey at specific time points to evaluate and monitor for the development of established side effects associated with pyridostigmine bromide administration.

Secondary Outcome Measures

Name	Time	Method
Number of participants with complications	30-day period following surgery	The number of participants with any type of complication or adverse event occurring within the first 30-days following surgery.
Time to tolerance of solid food after postoperative ileus	Time from the point of postoperative ileus diagnosis until first meal in which solid food is tolerated for up to 30 days	The amount of time (in minutes) from the participant being diagnosed with postoperative ileus confirmed with imaging findings until the first tolerance of solid food.
Number of participants requiring re-operation	30-day period following initial surgery	The number of participants who require a re-operation for any reason during the first 30-days following the initial operation.
Number of participants requiring re-admission	30-day period following surgery	The number of participants requiring re-admission to the hospital for any reason during the first 30-days following surgery.
Time to passage of stool after postoperative ileus diagnosis	Time from the point of postoperative ileus diagnosis until the first passage of stool for up to 30 days	The amount of time (in minutes) from the participant being diagnosed with postoperative ileus confirmed with imaging findings until the first passage of stool.

Trial Locations

Locations (1)

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States