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Completed

NCT Number: NCT02543658

Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

Acute pancreatitis(A) often complicated with Intra-abdominal Hypertension. After the onset of acute pancreatitis, capillary leakage causing ascites,upper gastrointestinal tract obstruction and paralytic ileus leading to an elevated IAP, severe IAH leads to ACS with high mortality. Neostigmine is an anti-cholinesterase drugs, can enhance intestinal peristalsis, promote flatus defecation. The aim of this study was to determine the effect of neostigmine on reducing abdominal pressure and clinical prognosis in patients with AP by promoting intestinal peristalsis and defecation.

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Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

About this study

Acute pancreatitis(AP) runs a severe course in around 20% of patients and is associated with a mortality up to 30%. Intra-abdominal hypertension(IAH)is a common complication of severe acute pancreatitis(SAP). The inflammation of the pancreas starts a cascade of pancreatic and visceral edema, acute peripancreatic fluid collections, capillary leakage causing ascites, paralytic ileus, and gastric dilatation by upper gastrointestinal tract obstruction leading to an elevated intra-abdominal pressure (IAP). A sustained or repeated pathological elevation in IAP ≥12 mmHg is defined as IAH, it generally occurs often within the first week after onset of SAP. Persistent and serious IAH (IAP >20 mmHg ) often leads to new onset organ failure or acute worsening of existing organ failure, which is defined as ACS and associated with a mortality rate of 49%.

In the past practice, many patients with ACS undergo decompressive laparotomy, which obviously has a risk of complications. Therefore, numerous medical, nonmedical, and minimally invasive therapies have been introduced. Neostigmine is an anti-cholinesterase drugs, can enhance intestinal peristalsis, promote flatus defecation. World Society for Abdominal Compartment Syndrome (WSACS)guidelines,suggest that neostigmine be used for the treatment of established colonic ileus not responding to other simple measures and associated with IAH.However, no data exist on the effects of pharmacologic promotility therapy on IAP or outcomes among those with IAH/ACS. The aim of this study was to evaluate the efficacy of neostigmine on reducing IAP in AP patients with IAH.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18-70 year ;
  • The diagnosis of acute pancreatitis according to the revised Atlanta classification.
  • IAH is defined as IAP ≥ 12 mmHg by the World Society of Abdominal;Compartment Syndrome (WSACS);
  • After 24 hours of conventional treatment(such as gastrointestinal decompression or percutaneous drainage of ascites), the IAP of AP patients with IAH was still ≥ 12 mmHg;
  • The onset time of acute pancreatitis was within 2 weeks;
  • Signed the informed consent.

Exclusion criteria

  • Previous history of laparotomy;
  • Mechanical ileus or abdominal hemorrhage were considered clinically;
  • Those who have contraindications to neostigmine: 1) Patients with angina; 2) myocardial infarction; 3) ventricular tachycardia; 4) bradycardia; 5) acute circulatory failure; 6) epilepsy; 7) bronchial asthma; 8) mechanical intestinal obstruction; 9) urinary tract infarction; 10) hyperthyroidism; 11) serious arrhythmia; 12) bladder operation; 13) intestinal fistula;
  • Allergic to neostigmine;
  • Pregnant or lactating patients.

Treatment and study plan

Neostigmine Methylsulfate 1 MG/ML

Drug

The initial dose was 1mg, intramuscular injection(IM) once every 12 hours. If there is no defecation after 12 hours, the dose is increased to 1mg IM once every 8 hours; if there is no defecation after 24 hours, the dose is increased to 1mg IM once every 6 hours. If the abdominal pressure drops below 12mmhg, neostigmine will be stopped, otherwise it will be used continuously for 7 days.

Other names: Prostigmin

Conservative treatment

Combination Product

Intragastric administration of paraffin oil, 50ml,once every 8 hours;gastrointestinal decompression with nasogastric tube and rectal tub; lycerin enema promotes defecation; patients with ascites undergo percutaneous puncture drainage. Other conservative medical treatment recommended by the guidelines.

Other names: Non-surgical treatment

Primary outcomes

  1. Percent Change of IAP After Treatment

    Time frame: From randomization to 7 days after treatment,Measured IAP every 6 hours

    Monitor the intra-abdominal pressure within 1 to 7 days after randomization, and calculate the percent change compared with that before randomization

Secondary outcomes

  1. The Change of Stool Volume at 1-7 Days After Randomization

    Time frame: From randomization to 7 days

    After randomization, the change of stool volume (ML) was calculated every 24 hours.For example, the amount of stool volume decreased or increased in 24 hours after grouping compared to before grouping.

  2. New-onset Abdominal Compartment Syndrom

    Time frame: From randomization to discharge or death, assessed up to 4 weeks

    Abdominal compartment syndrome is defined as a sustained IAP>20 mmHg (with or without an APP<60 mmHg) that is associated with new organ dysfunction/failure

  3. New-onset Organ Failure

    Time frame: From randomization to discharge or death, assessed up to 3 months

    Incidence of organ failure from randomization to discharge or death, assessed up to 3 months

  4. Death of 90 Days

    Time frame: From randomization to 90 days after onset.

    Death during from randomization to 90 days after onset.

  5. Timing of Enteral Nutrition

    Time frame: Start time of enteral nutrition after randomization, assessed up to 30 days

    From date of randomization to enteral nutrition, assessed up to 30 days

  6. Number of Participants With Deterioration of IAH

    Time frame: From randomization to 7 days

    IAP rebound ≥ 5mmHg or increase ≥ 20mmHg within 1-7 days after grouping

  7. Number of Participants With Adverse Effects on the Cardiovascular System

    Time frame: From randomization to 7 days

    Due to that neostigmine has an inhibitory effect on the cardiovascular system, new-onset cardiovascular failure after grouping is considered as a possible adverse event related to neostigmine.Cardiovascular failure was defined as circulatory systolic blood pressure <90 mm Hg, despite adequate fluid resuscitation, or need for inotropic catecholamine support

Other outcomes

  1. Days in Hospital

    Time frame: From randomisation to 6 months

    Days in hospital within 6 months after randomisation

  2. Days in ICU

    Time frame: From randomisation to 6 months

    Days in ICU within 6 months after randomisation

  3. Medical Expenses

    Time frame: From randomisation to 6 months

    Medical expenses within 6 months after randomisation

Sponsors and collaborators

Lead sponsor

The First Affiliated Hospital of Nanchang University

Other

Registry information

Official study title

The Curative Effect and Security of Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

Important dates

Study start
2015
Primary completion
2017
Study completion
2018
First posted
Sep 7, 2015
Registry last updated
Oct 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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