Pyridostigmine for Paralytic Ileus

(PESTI Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Stefan D Holubar

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Stefan Holubar MD MS FACS, FASCRS

Must not be taking: Acetylcholine esterase inhibitors, Laxatives

Disqualifiers: Bowel obstruction, Intraabdominal septic complications, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing pyridostigmine, a medication that helps muscles work better, as a treatment for patients who have developed postoperative ileus after colorectal surgery. Postoperative ileus is a condition where the intestines don't function properly after surgery. Pyridostigmine works by increasing levels of a chemical that helps muscles move, which may help the intestines work better. Pyridostigmine has been shown to help with conditions like chronic constipation.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including neostigmine, alvimopan, metoclopramide, erythromycin, methylnaltrexone, naloxegol, cisapride, and laxatives or cathartics. If you are currently using any of these, you would need to discontinue them to participate.

What data supports the effectiveness of the drug pyridostigmine for treating paralytic ileus?

Research shows that pyridostigmine, a drug that helps increase gut movement, significantly reduces the time it takes for patients to pass gas and stool after abdominal surgery compared to a placebo. In one study, 95% of patients treated with pyridostigmine responded within 24 hours, while only 50% of those given a placebo did. ^{1 2 3 4 5}

Is pyridostigmine safe for treating gastrointestinal issues?

Pyridostigmine has been studied for its safety in treating gastrointestinal issues, particularly after surgery, and is generally considered safe for use in humans. It works by increasing intestinal contractions, and studies have shown it to be effective in reducing the duration of postoperative ileus with no major safety concerns reported. ^{1 2 3 5 6}

How does the drug pyridostigmine differ from other treatments for paralytic ileus?

Pyridostigmine is unique because it works by increasing the availability of acetylcholine, a chemical that enhances gut movement, through a cholinergic anti-inflammatory pathway. This mechanism is different from other treatments, as it specifically targets the underlying cause of reduced gut motility, making it a potentially effective option for speeding up recovery after abdominal surgery. ^{1 2 3 7 8}

Research Team

Stefan D Holubar

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults who've had colorectal surgery and are now facing a condition called postoperative ileus, where the intestines don't move food properly causing bloating or nausea. Participants need to have normal organ function, not be pregnant or breastfeeding, and can't have other serious health issues like heart failure or bowel obstructions.

Inclusion Criteria

I am not completely bedridden.

I am an adult who had colorectal surgery and now have bloating and can't pass gas or stool for over 48 hours.

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

Exclusion Criteria

I do not have uncontrolled illnesses like severe asthma, heart failure, or major organ failure.

I am not currently using any experimental drugs or specific medications for digestion.

I have had infections inside my abdomen like abscesses or leaks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either pyridostigmine or placebo every 12 hours for a maximum of 48 hours

2 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including side effects and bowel function

30 days

Regular follow-up visits

Outcome Assessment

Assessment of re-operation, complications, and re-admission within 30 days post-surgery

30 days

Treatment Details

Interventions

• Placebo (Other)
• Pyridostigmine Bromide (Cholinesterase Inhibitor)

Trial Overview The study tests if Pyridostigmine Bromide can help with intestinal movement after surgery compared to a placebo. It's a double-blind trial, meaning neither patients nor doctors know who gets the real drug. Everyone continues standard care too.

Participant Groups

Group I: Pyridostigmine Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Patients randomized to this group will be given starch orally, every 12 hours for a maximum of 48 hours.

Who Is Running the Clinical Trial?

Stefan Holubar MD MS FACS, FASCRS

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

In a pilot study involving 15 patients who underwent elective colorectal surgery, oral pyridostigmine was found to be safe, with no adverse effects directly linked to its use and no signs of excessive parasympathetic activity.

The median time to recovery of gastrointestinal function, measured by the GI-2 score, was 2 days, suggesting potential benefits in GI motility, but further research with larger sample sizes is necessary to confirm its efficacy in preventing postoperative ileus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PyRICo-Pilot: pyridostigmine to reduce the duration of postoperative ileus after colorectal surgery - a phase II study. Dudi-Venkata, NN., Kroon, HM., Bedrikovetski, S., et al.[2021]

In a study of 40 patients, oral pyridostigmine (60 mg) significantly reduced the time to pass gas and stool after abdominal surgery, with mean times of 5.4 hours and 4.9 hours, respectively, compared to 32.4 hours and 36.2 hours in the control group.

Pyridostigmine was effective in 95% of patients within the first 24 hours, while only 50% of the control group responded, highlighting its potential as a simple and effective treatment for postoperative ileus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Effect of Oral Pyridostigmine on the Ileus after Abdominal Surgery: A Blinded Randomized Clinical Trial. Maleknejad, A., Khazaei, A., Bouya, S.[2020]

Acetylcholinesterase inhibitors, specifically neostigmine and pyridostigmine, may significantly reduce the time it takes for gastrointestinal function to return after abdominal surgery, with some studies showing a reduction of 17 to 47.6 hours in time to flatus or stool among 703 patients across 8 randomized controlled trials.

Despite the promising results, the current evidence is limited and potentially biased, highlighting the need for further research to confirm these findings and explore the integration of these inhibitors into enhanced recovery protocols, particularly for colorectal surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of acetylcholinesterase inhibitors in reducing time to gastrointestinal function recovery following abdominal surgery: A systematic review. Traeger, L., Dudi-Venkata, N., Bedrikovetski, S., et al.[2023]

In a study involving over 100 patients with functional ileus, a treatment combining adrenergic blockade with low doses of stimulants effectively restored intestinal function, particularly in patients resistant to traditional stimulant therapies.

The approach, which focuses on countering adrenergic inhibition rather than merely stimulating the intestines, demonstrated a low risk of complications and significant efficacy in treating functional ileus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of functional ileus: adrenergic blockade and stimulation (author's transl)]. Grund, KE.[2013]

In a case series of children with various gastrointestinal motility disorders, oral pyridostigmine was found to be effective and safe, improving symptoms like abdominal distention and bowel movement frequency.

The effective dosing of pyridostigmine ranged from 0.25 to 2.0 mg/kg/day, and while one patient experienced abdominal cramping, the overall results suggest it is a promising option when other treatments fail.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disorders: A Case Series. Manini, ML., Camilleri, M., Grothe, R., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

PyRICo-Pilot: pyridostigmine to reduce the duration of postoperative ileus after colorectal surgery - a phase II study. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Effect of Oral Pyridostigmine on the Ileus after Abdominal Surgery: A Blinded Randomized Clinical Trial. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Use of acetylcholinesterase inhibitors in reducing time to gastrointestinal function recovery following abdominal surgery: A systematic review. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ceruletide vs. metoclopramide in postoperative intestinal paralysis. A double-blind clinical trial. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of functional ileus: adrenergic blockade and stimulation (author's transl)]. [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disorders: A Case Series. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Use of neostigmine for the management of drug induced ileus in severe poisonings. [2013]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review. [2020]