Brief Title
Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis
Official Title
Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Proportion of positive bacterial cultures
Secondary Outcome
Postoperative hospital stay
Condition
Cholecystitis, Acute
Intervention
Piperacillin-tazobactam combination product
Study Arms / Comparison Groups
Intervention
Description: Piperacillin-tazobactam combination product
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
March 2009
Completion Date
January 2018
Primary Completion Date
December 2017
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Folke Hammarqvist, Ass Prof, ,
Location Countries
Sweden
Location Countries
Sweden
Administrative Informations
NCT ID
NCT02619149
Organization ID
AVAC
Responsible Party
Principal Investigator
Study Sponsor
Karolinska Institutet
Study Sponsor
Folke Hammarqvist, Ass Prof, Principal Investigator, Karolinska Institutet, CLINTEC, Stockholm
Verification Date
March 2018