Cholecystitis, AcutePhase 3AVACNCT02619149
Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis
A Phase 3 study testing Piperacillin-tazobactam combination product and Saline solution in people with Cholecystitis, Acute, run by Karolinska Institutet at 1 site in Sweden.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholecystitis, Acute
- What is being tested?
- Piperacillin-tazobactam combination product and Saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteSweden
- Study dates
- Mar 2009to Jan 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical and radiologic signs of acute cholecystitis
- First acute symptoms occurring within five days before surgery
Who cannot join
- Anamnesis exceeding five days
- Any contraindication for laparoscopic surgery
- Allergy against beta-lactame antibiotics
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Karolinska University Hospital, Center for Digestive Diseases
Stockholm, 14186
About this study
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.
Read the 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.
- Conditions
- Cholecystitis, Acute
- Being tested
- Piperacillin-tazobactam combination product, Saline solution
- Medical subject headings
- Cholecystitis, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin-tazobactam combination productDrug
Also called Piperacillin-Tazobactam
Piperacillin-Tazobactam (extended-spectrum, beta-lactamase inhibitor) iv peroperatively as prophylaxis
Saline solutionDrug
Saline iv as placebo control
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Active comparator | Piperacillin-tazobactam combination product Receives: Drug: Piperacillin-tazobactam combination product |
| Control | Placebo comparator | Saline solution Receives: Drug: Saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of positive bacterial cultures
Proportion of patients with bacterial growth in the bile, assessed by culture from the bile assembled perioperatively.
Measured: 5 days
Secondary outcomes (6)
Postoperative hospital stay
Measured: 5-10 days
Health-related quality of life
Health-related quality of Life measured with SF-3
Measured: One month
Postoperative pain as measured by the McGill Pain Questionnaire
Level of pain as measured by the McGill Pain Questionnaire
Measured: 3 days
Levels of C-reactive Protein postoperatively
CRP levels measured daily in the postoperative period
Measured: 3 days
Surgical site infections
Abscesses or superficial wound infections requiring drainage or antibiotic treatment
Measured: 5-10 days
Infectious complications other than surgical site infections
Measured: 5-10 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2015 (estimated)
- Study startMar 2009
- Primary completionDec 2017
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cholecystitis, AcuteStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gabriel Sandblom, Karolinska Institutet
- Investigators
- Folke Hammarqvist, Ass Prof, Principal investigator, Karolinska Institutet, CLINTEC, Stockholm
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02619149
- Sponsor's protocol ID
- AVAC
- Acronym
- AVAC
- Status last verified
- Mar 2018
- First submitted
- 26 Nov 2015
- Last updated
- 6 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Jaafar G, Sandblom G, Lundell L, Hammarqvist F. Antibiotic prophylaxis in acute cholecystectomy revisited: results of a double-blind randomised controlled trial. Langenbecks Arch Surg. 2020 Dec;405(8):1201-1207. doi: 10.1007/s00423-020-01977-x. Epub 2020 Aug 29.
PubMed 32860109
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Piperacllin Versus Placebo in Patients Undergoing Surgery for Acute Cholecystitis
- ClinicalTrials.gov ID
- NCT02619149
- Acronym / sponsor ID
- AVAC / AVAC
- Conditions
- Cholecystitis, Acute
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Study start
- Mar 2009
- Primary completion
- Dec 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 2 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Active comparator | Drug: Piperacillin-tazobactam combination productPiperacillin-tazobactam combination product |
| Control | Placebo comparator | Drug: Saline solutionSaline solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Clinical and radiologic signs of acute cholecystitis
- First acute symptoms occurring within five days before surgery
Key exclusion criteria (3 listed)
- Anamnesis exceeding five days
- Any contraindication for laparoscopic surgery
- Allergy against beta-lactame antibiotics
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin-tazobactam combination productAlso: Piperacillin-TazobactamPiperacillin-Tazobactam (extended-spectrum, beta-lactamase inhibitor) iv peroperatively as prophylaxis | Drug | Intervention |
| Saline solutionSaline iv as placebo control | Drug | Control |
Primary outcome
Proportion of positive bacterial cultures
Time frame: 5 days
Proportion of patients with bacterial growth in the bile, assessed by culture from the bile assembled perioperatively.
6 secondary outcomes
Postoperative hospital stay
Time frame: 5-10 days
Health-related quality of life
Time frame: One month
Postoperative pain as measured by the McGill Pain Questionnaire
Time frame: 3 days
Levels of C-reactive Protein postoperatively
Time frame: 3 days
Surgical site infections
Time frame: 5-10 days
Infectious complications other than surgical site infections
Time frame: 5-10 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2018.
- Derived from this study: PubMed 32860109Jaafar G, Sandblom G, Lundell L, Hammarqvist F. Antibiotic prophylaxis in acute cholecystectomy revisited: results of a double-blind randomised controlled trial. Langenbecks Arch Surg. 2020 Dec;405(8):1201-1207. doi: 10.1007/s00423-020-01977-x. Epub 2020 Aug 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Folke Hammarqvist, Ass Prof principal investigator
Karolinska Institutet, CLINTEC, Stockholm
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Piperacillin-tazobactam combination product and Saline solution in people with Cholecystitis, Acute, run by Karolinska Institutet at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of positive bacterial cultures (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02619149, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2018.