Neostigmine Treatment of Acute Pancreatitis Combined With Intra-abdominal Hypertension

NCT02543658 | Completed Phase 2 Results

• 1 other identifier: FAHONCU
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Pancreatitis; Intra-abdominal Hypertension

Keywords

Acute Pancreatitis; Intra-abdominal hypertension; Abdominal compartment syndrome; Curative Effect; Security; Neostigmine

Outcome Measures

Primary Outcomes (1)

• Percent Change of IAP After Treatment

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

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

Secondary Outcomes (7)

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

  From randomization to 7 days

• New-onset Abdominal Compartment Syndrom

  From randomization to discharge or death, assessed up to 4 weeks

• New-onset Organ Failure

  From randomization to discharge or death, assessed up to 3 months

• Death of 90 Days

  From randomization to 90 days after onset.

• Timing of Enteral Nutrition

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

Other Outcomes (3)

• Days in Hospital

  From randomisation to 6 months

• Days in ICU

  From randomisation to 6 months

• Medical Expenses

  From randomisation to 6 months

Study Arms (2)

Neostigmine

EXPERIMENTAL

Intramuscular injection of neostigmine on the basis of conventional conservative treatment

Drug: Neostigmine Methylsulfate 1 MG/ML; Combination Product: Conservative treatment

Conservative treatment

OTHER

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.

Combination Product: Conservative treatment

Interventions

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.

Also known as: Prostigmin

Neostigmine

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.

Also known as: Non-surgical treatment

Conservative treatment; Neostigmine

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Nanchang University: lead

Study Sites (1)

Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

Related Publications (12)

• Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.

  PMID: 23100216 BACKGROUND

• Vidal MG, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, Canales H, Reina R, Estenssoro E. Incidence and clinical effects of intra-abdominal hypertension in critically ill patients. Crit Care Med. 2008 Jun;36(6):1823-31. doi: 10.1097/CCM.0b013e31817c7a4d.

  PMID: 18520642 BACKGROUND

• Kasi PM. The use of intravenous neostigmine in palliation of severe ileus. Case Rep Gastrointest Med. 2013;2013:796739. doi: 10.1155/2013/796739. Epub 2013 Feb 14.

  PMID: 23476830 BACKGROUND

• Tracey KJ. The inflammatory reflex. Nature. 2002 Dec 19-26;420(6917):853-9. doi: 10.1038/nature01321.

  PMID: 12490958 BACKGROUND

• Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000 May 25;405(6785):458-62. doi: 10.1038/35013070.

  PMID: 10839541 BACKGROUND

• Schneider L, Jabrailova B, Soliman H, Hofer S, Strobel O, Hackert T, Buchler MW, Werner J. Pharmacological cholinergic stimulation as a therapeutic tool in experimental necrotizing pancreatitis. Pancreas. 2014 Jan;43(1):41-6. doi: 10.1097/MPA.0b013e3182a85c21.

  PMID: 24212240 BACKGROUND

• Shaikh N, Kettern MA, Hanssens Y, Elshafie SS, Louon A. A rare and unsuspected complication of Clostridium difficile infection. Intensive Care Med. 2008 May;34(5):963-6. doi: 10.1007/s00134-007-0922-6. Epub 2007 Nov 20.

  PMID: 18026931 BACKGROUND

• Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain ML, De Keulenaer B, Duchesne J, Bjorck M, Leppaniemi A, Ejike JC, Sugrue M, Cheatham M, Ivatury R, Ball CG, Reintam Blaser A, Regli A, Balogh ZJ, D'Amours S, Debergh D, Kaplan M, Kimball E, Olvera C; Pediatric Guidelines Sub-Committee for the World Society of the Abdominal Compartment Syndrome. Intra-abdominal hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013 Jul;39(7):1190-206. doi: 10.1007/s00134-013-2906-z. Epub 2013 May 15.

  PMID: 23673399 BACKGROUND

• van Brunschot S, Schut AJ, Bouwense SA, Besselink MG, Bakker OJ, van Goor H, Hofker S, Gooszen HG, Boermeester MA, van Santvoort HC; Dutch Pancreatitis Study Group. Abdominal compartment syndrome in acute pancreatitis: a systematic review. Pancreas. 2014 Jul;43(5):665-74. doi: 10.1097/MPA.0000000000000108.

  PMID: 24921201 BACKGROUND

• Trikudanathan G, Vege SS. Current concepts of the role of abdominal compartment syndrome in acute pancreatitis - an opportunity or merely an epiphenomenon. Pancreatology. 2014 Jul-Aug;14(4):238-43. doi: 10.1016/j.pan.2014.06.002. Epub 2014 Jun 17.

  PMID: 25062870 BACKGROUND

• Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med. 1999 Jul 15;341(3):137-41. doi: 10.1056/NEJM199907153410301.

  PMID: 10403850 BACKGROUND

• He W, Chen P, Lei Y, Xia L, Liu P, Zhu Y, Zeng H, Wu Y, Ke H, Huang X, Cai W, Sun X, Huang W, Sutton R, Zhu Y, Lu N. Randomized controlled trial: neostigmine for intra-abdominal hypertension in acute pancreatitis. Crit Care. 2022 Mar 3;26(1):52. doi: 10.1186/s13054-022-03922-4.

  PMID: 35241135 DERIVED

MeSH Terms

Conditions

Pancreatitis; Intra-Abdominal Hypertension

Interventions

Neostigmine; Conservative Treatment

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Compartment Syndromes; Muscular Diseases; Musculoskeletal Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Therapeutics

Results Point of Contact

• Title: Wenhua He
• Organization: First affilitated hospital of Nanchang university

hewenhua@ncu.edu.cn

+8613879182642

Study Officials

• Nonghua Lv, MD

  the Frist Affiliated Hospital of Nanchang University

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician-in-charge

Study Record Dates

• First Submitted: August 27, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: August 15, 2017
• Study Completion: May 30, 2018
• Last Updated: October 5, 2021
• Results First Posted: August 6, 2020

Record last verified: 2021-10

Locations

CN (1)