Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis

Phase 3

Completed

• Conditions: Cholecystitis, Acute
• Interventions: Drug: Piperacillin-tazobactam combination product; Drug: Saline solution

• Registration Number: NCT02619149
• Lead Sponsor: Karolinska Institutet

Brief 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.

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2009-03
• Study First Submitted: 2015-11-26
• Study First Submitted QC: 2015-12-01
• Study First Posted: 2015-12-02
• Primary Completion: 2017-12
• Study Completion: 2018-01
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-05
• Last Update Posted: 2018-03-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Clinical and radiologic signs of acute cholecystitis
• First acute symptoms occurring within five days before surgery

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Exclusion Criteria

• Anamnesis exceeding five days
• Any contraindication for laparoscopic surgery
• Allergy against beta-lactame antibiotics

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Piperacillin-tazobactam combination product	Piperacillin-tazobactam combination product
Control	Saline solution	Saline solution

Primary Outcome Measures

Name	Time	Method
Proportion of positive bacterial cultures	5 days	Proportion of patients with bacterial growth in the bile, assessed by culture from the bile assembled perioperatively.

Secondary Outcome Measures

Name	Time	Method
Postoperative hospital stay	5-10 days
Surgical site infections	5-10 days	Abscesses or superficial wound infections requiring drainage or antibiotic treatment
Levels of C-reactive Protein postoperatively	3 days	CRP levels measured daily in the postoperative period
Postoperative pain as measured by the McGill Pain Questionnaire	3 days	Level of pain as measured by the McGill Pain Questionnaire
Health-related quality of life	One month	Health-related quality of Life measured with SF-3
Infectious complications other than surgical site infections	5-10 days

Trial Locations

Locations (1)

Karolinska University Hospital, Center for Digestive Diseases; 🇸🇪 Stockholm, Sweden