Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis

Cholecystitis, Acute Clinical Trial

— AVAC  

Official title:

Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02619149
• Other study ID #: AVAC
• Status: Completed
• Phase: Phase 3
• First received: November 26, 2015
• Last updated: March 5, 2018
• Start date: March 2009
• Est. completion date: January 2018

Study information

• Verified date: March 2018
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The benefit from antibiotic prophylaxis in patients undergoing laparoscopic cholecystectomy for acute cholecystitis is insufficiently known. The aim of the present double-blind randomized controlled is to compare piperacilin with placebo in patients undergoing cholecystectomy for acute cholecystitis with anamnesis not exceeding 5 days. Altogether 100 patients are intended to be included. Primary endpoint is biliary contamination. Secondary endpoints are postoperative hospital stay, health-related quality of life, pain perception, postoperative markers of inflammatory response, surgical site infections, infectious complications other than surgical site infections, health economy and relationship between symptom anamnesis and bile contamination.

Description:

Background

Inflammation in the gallbladder due to obstruction of gallstones (acute cholecystitis) is a common condition and one of the most common indications for laparoscopic cholecystectomy. In most cases, the procedure may be performed without great risk of severe complications. In some cases, however, the congested bile in the gallbladder may become infected.

In clinical routine, acute cholecystitis is often managed as an infectious condition, despite the fact that previous studies have shown that the bile in most cases of acute cholecystitis is sterile. On the other hand, antibiotic prophylaxis may reduce the risk of surgical site infections in those cases when there is a manifest bacterial contamination and, perhaps, also reduce the risk of contamination. There is firm evidence supporting acute surgery, prefereably laparoscopic cholecystectomy, but the benefit from antibiotic treatment has not been full evaluated.

Previous studies have shown that the benefit from antibiotic prophylaxis is very limited in case of laparoscopic cholecystectomy for uncomplicated gallstone disease. There are, however, very few studies that have assessed antibiotic prophylaxis in surgery for acute cholecystitis.

The aim of the present study is to assess the benefit of antibiotic prophylaxis in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.

Methods The study is based on patients admitted for acute cholecystitis at the department of acute surgery, Karolinska University Hospital Huddinge. In case the patients fulfill the inclusion critera and are suitable for laparoscopic surgery, written and oral information about the study is given.

In case they agree to participate in the study, treatment allocation is determined by a sealed envelope system. The patients are randomised to receive either Piperacillin 4g x 3 iv preoperatively as prophylaxis or placebo (saline infusion). The study is double-blind. Piperacillin/placebo is administrated by a research nurse after allocation. The infusion is covered by a bag in order to maintain blinding. Neither the surgeon performing the procedure, nor the patient or staff caring for the patient are informed about the allocation. The procedure should be performed within 24 days after inclusion. Administration of Piperacillin/placebo is started immediately after inclusion and continued until the procedure is completed.

If a categorical indication for antibiotic treatment occurs during surgery, the allocated infusion is removed and the patient is given antibiotic as decided by the surgeon. In such cases, the patient stays in the study and is analysed according to an intention to treat.

During the laparoscopic cholecystectomy, at least 10 cc of bile is aspirated under sterile conditions from the fundus of the gallbladder with a long needle before the start of the peritoneum dissection. The bile is sent for aerobic and anaerobic culture. Bacteria are identified using standard laboratory procedures.

Sample size estimation If the incidence of positive cultures is 50% and in the placebo group and this is reduced to 25% if antibiotic prophylaxis is given, 36 patients in each arm would be required in order to reach 80% chance of detecting this difference at a p<0.05 level of significance (one sided test). A total sample of 100 patients should thus be sufficient to test the primary outcome measure.

Follow-up Samples for CRP, interleukins, bilirubin, AST, ALT and ALP are taken daily from the peroperative day until postoperative day 2.

Quality of life is assessed by SF-36 preoperatively. Level of pain is estimated based on the MacGill Pain Questionnaire from the day of the procedure until postoperative day 2.

One month postoperatively, the patient is invited to follow-up. At follow-up, SF-36 is filled in.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Clinical and radiologic signs of acute cholecystitis

• First acute symptoms occurring within five days before surgery

Exclusion Criteria:

• Anamnesis exceeding five days

• Any contraindication for laparoscopic surgery

• Allergy against beta-lactame antibiotics

Related Conditions & MeSH terms

• Cholecystitis
• Cholecystitis, Acute

Intervention

Drug:
• Piperacillin-tazobactam combination product
Piperacillin-Tazobactam (extended-spectrum, beta-lactamase inhibitor) iv peroperatively as prophylaxis
• Saline solution
Saline iv as placebo control

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital, Center for Digestive Diseases	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of positive bacterial cultures	Proportion of patients with bacterial growth in the bile, assessed by culture from the bile assembled perioperatively.	5 days
Secondary	Postoperative hospital stay		5-10 days
Secondary	Health-related quality of life	Health-related quality of Life measured with SF-3	One month
Secondary	Postoperative pain as measured by the McGill Pain Questionnaire	Level of pain as measured by the McGill Pain Questionnaire	3 days
Secondary	Levels of C-reactive Protein postoperatively	CRP levels measured daily in the postoperative period	3 days
Secondary	Surgical site infections	Abscesses or superficial wound infections requiring drainage or antibiotic treatment	5-10 days
Secondary	Infectious complications other than surgical site infections		5-10 days