Extended Antibiotic Therapy in Postoperative of Laparoscopic Cholecystectomy in Acute Cholecystitis

Extended Antibiotic Therapy in Postoperative of Laparoscopic Cholecystectomy Due to Acute Cholecystitis. Is it Necessary?

Acute cholecystitis (AC) is a very common complication of cholelithiasis, encountered in 20% of symptomatic patients.

Nowadays laparoscopic cholecystectomy (LC) is the standard treatment in mild and moderates forms of diseases and antibiotic therapy in the postoperatory of these patients remains under discussion. However in the beginning, AC presents itself as an steril process, the obstruction of the cystic duct initiates a cascade of inflammation, ischaemia and necrosis, as well as bacterial proliferation within the gallbladder lumen. Bactibilia was a significant factor associated with total, as well as infectious, operative complications. Regarding this, for some authors, monotherapy with amoxicillin clavulanic (AMC) would be the best treatment after LC in patients with mild and moderate cholecystitis without intraoperative complications such as bile peritonitis, cholangitis, gallbladder perforation or abscess. In the other hand, others do not prescribe antimicrobial treatment after surgery in these selected patients.

There is controversy regarding the postoperative treatment with antibiotics in patients with mild and moderate cholecystitis and all the evidence about this topic.

Therefore, investigators decided to conduct a prospective randomized study in patients undergoing laparoscopic cholecystectomy for acute mild and moderate cholecystitis cancer. The patients will be randomized to receive AMC or placebo after surgery. With this study investigators intend to prove that are no clinical differences in postoperative outcomes between patients treated with AMC and placebo.

The primary aim of the trial is to assess that there are no benefits in the use of postoperative antibiotics in patients whit mild or moderate acute cholecystitis in whom a laparoscopic cholecystectomy was performed.

Study Overview

• Status: Completed
• Conditions: Acute Cholecystitis
• Intervention / Treatment: Drug: Amoxicillin clavulanic; Drug: Placebo

Detailed Description

Double blind randomized clinical trial

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1199
      • Hospital Italiano de Buenos Aires

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 to 85 years old
• Patients with diagnose of mild or moderate acute cholecystitis.
• Underwent laparoscopic cholecystectomy on Italian Hospital of Buenos Aires

Exclusion Criteria:

• They refuse to participate from the trial or the process of informed consent.
• Have known allergies or hypersensitivity to Mosapride or lactose (used for placebo).
• Patients with severe cholecystitis
• Patients with moderate cholecystitis who presents liver abscess, gallbladder abscess, cholangitis or bile peritonitis.
• Intraoperative findings like liver cancer, liver metastases, common bile duct stones or gallbladder carcinoma.
• Patients with conversion to laparotomy
• Previous treatment with antibiotics for more than five days.
• Patients with active oncological diseases, AIDS, diabetes, transplanted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (Amoxicillin Clavulanic); Intake of active drug (Amoxicillin Clavulanic). 3 g per day divided into 3 oral intakes of 1 g each (2 pill of Amoxicillin Clavulanic every 8 hrs). This treatment will begin on postoperative day 1 for 5 days.	Drug: Amoxicillin clavulanic; 3 g per day divided into 3 oral intakes of 1 g each (2 pill of Amoxicillin Clavulanic every 8 hrs). This treatment will begin on postoperative day 1 for 5 days.; Other Names: Optamox
Placebo Comparator: Placebo; Intake of placebo (Lactose). 1 pill of the same characteristics as Amoxicillin clavulanic every 8 hs. This will begin on postoperative day 1 for 5 days.	Drug: Placebo; 1 pill of the same characteristics as Amoxicillin clavulanic every 8 hs. This will begin on postoperative day 1 for 5 days.; Other Names: Lactose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of infectious postoperative complications	Incidence of infectious postoperative complications in patients who underwent a laparoscopic cholecystectomy due to acute mild and moderate cholecystitis, with antibiotics or placebo	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of hospital stay or readmissions.	To evaluate hospital stay.	30 days
Number of surgical reinterventions or reoperations.		30 days

Collaborators and Investigators

• Sponsor: Hospital Italiano de Buenos Aires
• Investigators: Principal Investigator: Martin de Santibañes, MD, Hospital Italiano de Buenos Aires; Study Director: Diego Giunta, MD, Hospital Italiano de Buenos Aires

Publications and helpful links

General Publications

• Clavien PA, Barkun J, de Oliveira ML, Vauthey JN, Dindo D, Schulick RD, de Santibanes E, Pekolj J, Slankamenac K, Bassi C, Graf R, Vonlanthen R, Padbury R, Cameron JL, Makuuchi M. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009 Aug;250(2):187-96. doi: 10.1097/SLA.0b013e3181b13ca2.
• Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373-83. doi: 10.1016/0021-9681(87)90171-8.
• Strasberg SM. Clinical practice. Acute calculous cholecystitis. N Engl J Med. 2008 Jun 26;358(26):2804-11. doi: 10.1056/NEJMcp0800929. No abstract available. Erratum In: N Engl J Med. 2008 Jul 17;359(3):325.
• Yoshida M, Takada T, Kawarada Y, Tanaka A, Nimura Y, Gomi H, Hirota M, Miura F, Wada K, Mayumi T, Solomkin JS, Strasberg S, Pitt HA, Belghiti J, de Santibanes E, Fan ST, Chen MF, Belli G, Hilvano SC, Kim SW, Ker CG. Antimicrobial therapy for acute cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg. 2007;14(1):83-90. doi: 10.1007/s00534-006-1160-y. Epub 2007 Jan 30.
• Yildiz B, Abbasoglu O, Tirnaksiz B, Hamaloglu E, Ozdemir A, Sayek I. Determinants of postoperative infection after laparoscopic cholecystectomy. Hepatogastroenterology. 2009 May-Jun;56(91-92):589-92.
• Yokoe M, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Gomi H, Pitt HA, Gouma DJ, Garden OJ, Buchler MW, Kiriyama S, Kimura Y, Tsuyuguchi T, Itoi T, Yoshida M, Miura F, Yamashita Y, Okamoto K, Gabata T, Hata J, Higuchi R, Windsor JA, Bornman PC, Fan ST, Singh H, de Santibanes E, Kusachi S, Murata A, Chen XP, Jagannath P, Lee S, Padbury R, Chen MF; Tokyo Guidelines Revision Committee. New diagnostic criteria and severity assessment of acute cholecystitis in revised Tokyo Guidelines. J Hepatobiliary Pancreat Sci. 2012 Sep;19(5):578-85. doi: 10.1007/s00534-012-0548-0.
• Kanafani ZA, Khalife N, Kanj SS, Araj GF, Khalifeh M, Sharara AI. Antibiotic use in acute cholecystitis: practice patterns in the absence of evidence-based guidelines. J Infect. 2005 Aug;51(2):128-34. doi: 10.1016/j.jinf.2004.11.007. Epub 2005 Jan 20.
• Grande M, Torquati A, Farinon AM. Wound infection after cholecystectomy. Correlation between bacteria in bile and wound infection after operation on the gallbladder for acute and chronic gallstone disease. Eur J Surg. 1992 Feb;158(2):109-12.
• Galili O, Eldar S Jr, Matter I, Madi H, Brodsky A, Galis I, Eldar S Sr. The effect of bactibilia on the course and outcome of laparoscopic cholecystectomy. Eur J Clin Microbiol Infect Dis. 2008 Sep;27(9):797-803. doi: 10.1007/s10096-008-0504-8. Epub 2008 Mar 28.
• Pellegrini P, Campana JP, Dietrich A, Goransky J, Glinka J, Giunta D, Barcan L, Alvarez F, Mazza O, Sanchez Claria R, Palavecino M, Arbues G, Ardiles V, de Santibanes E, Pekolj J, de Santibanes M. Protocol for extended antibiotic therapy after laparoscopic cholecystectomy for acute calculous cholecystitis (Cholecystectomy Antibiotic Randomised Trial, CHART). BMJ Open. 2015 Nov 18;5(11):e009502. doi: 10.1136/bmjopen-2015-009502.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): March 1, 2017
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Acute cholecystitis.; Amoxicillin clavulanic
• Additional Relevant MeSH Terms: Digestive System Diseases; Gallbladder Diseases; Biliary Tract Diseases; Cholecystitis; Acalculous Cholecystitis; Cholecystitis, Acute; Anti-Infective Agents; Anti-Bacterial Agents; Amoxicillin
• Other Study ID Numbers: 2111

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No