Using pyridostigmine to treat postoperative ileus after colorectal surgery

Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery (PESTI Trial)

This study is testing if a medication called pyridostigmine can help people who have bloating and no bowel movements after colorectal surgery feel better.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Cleveland Clinic (other)
• Locations: 1 site (Cleveland, Ohio)
• Trial ID: NCT05334485 on ClinicalTrials.gov

What this trial studies

This clinical trial is a double-blind, placebo-controlled, randomized trial assessing the safety and efficacy of pyridostigmine as a rescue therapy for postoperative ileus in patients who have undergone elective colorectal surgery. Eligible participants will be those who develop symptoms of ileus, such as bloating and absence of bowel movement, after their surgery. Patients will be randomly assigned to receive either pyridostigmine or a placebo, alongside standard care, and will be monitored for side effects using a specific scale. The study aims to determine if pyridostigmine can effectively alleviate postoperative ileus symptoms.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and over who have undergone elective colorectal resections and developed postoperative ileus.

Not a fit: Patients who do not develop postoperative ileus or have severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery times and patient comfort after colorectal surgery.

How similar studies have performed: Other studies have explored similar interventions for postoperative ileus, but the specific use of pyridostigmine in this context is less common and may provide novel insights.

Eligibility criteria

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

Where this trial is running

Cleveland, Ohio

• Cleveland Clinic Main Campus — Cleveland, Ohio, United States (RECRUITING)

Study contacts

• Principal investigator: Stefan D Holubar — The Cleveland Clinic
• Study coordinator: Stefan D Holubar

Conditions: Postoperative Ileus