Clinical trial NCT05334485: Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery
Official title: Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery (PESTI Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Postoperative Ileus
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2022-04-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Time until return of bowel function
timeFrame: Time from administration of pyridostigmine bromide or placebo until first passage of flatus for up to 30 days
measure: Incidence of pyridostigmine bromide associated side effects
timeFrame: Participants will complete the survey at enrollment and then again at 30 minutes following each administration of either pyridostigmine bromide or placebo.
Secondary outcomes:
measure: Time to passage of stool after postoperative ileus diagnosis
timeFrame: Time from the point of postoperative ileus diagnosis until the first passage of stool for up to 30 days
measure: Time to tolerance of solid food after postoperative ileus
timeFrame: Time from the point of postoperative ileus diagnosis until first meal in which solid food is tolerated for up to 30 days
measure: Number of participants with complications
timeFrame: 30-day period following surgery
measure: Number of participants requiring re-operation
timeFrame: 30-day period following initial surgery
measure: Number of participants requiring re-admission
timeFrame: 30-day period following surgery
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Stefan D Holubar
role: PRINCIPAL_INVESTIGATOR
References: