Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis
Primary Purpose
Surgical Site Infection
Status
Completed
Phase
Phase 4
Locations
Switzerland
Study Type
Interventional
Intervention
Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)
Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)
Sponsored by
About this trial
This is an interventional prevention trial for Surgical Site Infection
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Inpatient visceral, vascular and trauma procedures
- SAP indicated according to clinical standards (CDC guidelines for surgical wound classification)
- informed consent
Exclusion Criteria:
- Contraindication for study drugs
- Pre-existing antibiotic therapy within 14 days of surgery
- Any doubt that patients can make the decision to participate fully informed due to cognitive impairment, such as in critically ill or demented patients.
- Emergency procedures with planned incision within 2 hours after the surgeon indicated the procedure
- Participation in other studies that could potentially interfere with the present one (according to the ethics committee)
- Combined surgery including surgical subspecialties other than the above mentioned
Sites / Locations
- University Hospital Basel
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Early Prophylaxis
Late Prophylaxis
Arm Description
Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)
Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)
Outcomes
Primary Outcome Measures
Surgical Site Infection (SSI)
Surgical Site Infection within 30 days after index surgery
Secondary Outcome Measures
All-cause 30 day mortality
Length of hospital stay
Economic burden of SSI
Nosocomial infections
In-hospital complications
according to the Clavien-Dindo-Classification
Surgical Site Infection (SSI)
Surgical Site Infection within 1 year after surgery only for implant surgeries
Full Information
NCT ID
NCT01790529
First Posted
February 5, 2013
Last Updated
September 28, 2016
Sponsor
University Hospital, Basel, Switzerland
Collaborators
Cantonal Hospital of Aarau, Switzerland
1. Study Identification
Unique Protocol Identification Number
NCT01790529
Brief Title
Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis
Official Title
Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
September 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
Cantonal Hospital of Aarau, Switzerland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Surgical site infections (SSI) are the most frequent hospital acquired infections in patients who underwent surgery. With regards to the increasing financial restraint in patient care, the socio-economic burden of SSI in the public health sector and its prevention gains in importance.
The prophylactic application of antibiotics (surgical antimicrobial prophylaxis, SAP) prior to the skin incision significantly reduces the risk of SSI, but the correct time point of drug administration remains unclear. Most studies recommend application of SAP directly prior to skin incision. Other studies, however, suggest that this is too late and more time between administration of the SAP and skin incision is necessary for optimal SSI prevention. A large cohort study in Switzerland concluded that SAP should be applied between 74 and 30 minutes prior to skin incision.
Due to the obvious importance of this controversy, we want to answer this question with a clinical study (randomized controlled trial, RCT) at the University Hospital of Basel and the Cantonal Hospital of Aarau. We plan to investigate two administration strategies according to the timing of the SAP. Strategy A will consist of SAP application in the anesthetic room located in front of the actual operating theatre, where the patient gets anesthesia. Therefore, the application of SAP will take place early, approximately between 75 and 30 minutes prior to skin incision. In strategy B we will apply SAP in the operating theatre, which on average occurs later (approximately within the last 30 minutes before skin incision).
We test the hypothesis that strategy A is more effective in preventing SSI than strategy B. We will include a total of 5000 patients in abdominal, vascular and trauma surgery (2500 at each study site and 2500 per study group). All patients will be followed in the hospital for SSI occurrence. Additionally, all patients will be interviewed by telephone after hospital discharge at a defined follow-up period of 30 days (1 year if an implant is in place, such as hip endoprosthesis or meshes). We expect this study to be completed within approximately 3 years.
Detailed Description
Additionally, the association between the following pre-defined variables and the occurence of SSI, mortality, morbidity and length of hospital stay (LOS) will be investigated:
laparoscopy
tutorial assistance during operation
obesity (Body Mass Index, BMI)
preoperative Virtual Reality (VR) training
Adherence to Enhanced Recovery After Surgery (ERAS) concept
smoking status
perioperative blood glucose levels
preoperative levels of HbA1c
intensified insulin resistance as measured by Homeostasis Model Assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI)
type of diabetes (IDDM vs. NIDDM)
intraoperative Hypothermia (body core temperature)
Lack of adherence to the principles of asepsis during surgery
surgical experience
patients age
Malnutrition, measured by Hypalbuminaemia
emergency operations
immunosuppression and steroids
Predictive value of Procalcitonin
American Society of Anesthesiologists (ASA) classification
intraoperative blood transfusion
preoperative wound class
Amendments:
The following changes were made to the study protocol according to amendments approved by the local ethics committee:
As of April 22nd, 2013, or the 222. patient randomized at the University Hospital Basel, the time the SAP infusion STARTED was recorded instead of the time that it ENDED. The decision to change this important parameter was taken in order to make results of this trial more comparable to those of other published studies.
In the original study protocol it was planned to provide each randomized patient with a patient's diary to record signs of SSI. This was abandoned for limited benefit and in order to minimize patients' time and effort.
Patients who undergo combined surgery (by one of the participating surgical specialties plus by a non participating specialty) shall not be included in this trial as outcomes (SSI) could be difficult to correlate to one or another part of surgery. This had not been specified as an exclusion criterion in the original study protocol.
Patients' information sheets and informed consents in one of the languages other than German were only approved by the local ethics committees by May 15th, 2013.
As per ethics committees regulations, patients can only be included in more than one clinical trials under specific circumstances. Therefore only a limited percentage of patients that are already included in other studies can still be included for this trial. However, overall, this only excludes a very limited number of potentially includable patients.
The following additional amendments were authorized by the ethics committees on August 9th, 2014:
- Version 4 of the patients' information and the written consent form. In these new versions, patients are specifically asked for permission to review their general practitioners' notes concerning potential SSI, for planned follow up as well as in case of readmission to hospital. This is specified in the study protocol, but had not been specifically mentioned in the patients' information and consent forms. This change is also intended to significantly decrease the number of patients lost to follow up as it proved difficult to contact some patients by telephone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
5000 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Early Prophylaxis
Arm Type
Experimental
Arm Description
Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)
Arm Title
Late Prophylaxis
Arm Type
Active Comparator
Arm Description
Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)
Intervention Type
Procedure
Intervention Name(s)
Early administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in anesthetic room (75 to 30 minutes prior to skin incision)
Intervention Type
Procedure
Intervention Name(s)
Late administration of SAP (Cefuroxime (plus metronidazole in colorectal surgery)) in the operating theatre (within 30 minutes prior to skin incision)
Primary Outcome Measure Information:
Title
Surgical Site Infection (SSI)
Description
Surgical Site Infection within 30 days after index surgery
Time Frame
30 days
Secondary Outcome Measure Information:
Title
All-cause 30 day mortality
Time Frame
30 days
Title
Length of hospital stay
Time Frame
1 year
Title
Economic burden of SSI
Time Frame
1 year
Title
Nosocomial infections
Time Frame
1 year
Title
In-hospital complications
Description
according to the Clavien-Dindo-Classification
Time Frame
1 year
Title
Surgical Site Infection (SSI)
Description
Surgical Site Infection within 1 year after surgery only for implant surgeries
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Inpatient visceral, vascular and trauma procedures
SAP indicated according to clinical standards (CDC guidelines for surgical wound classification)
informed consent
Exclusion Criteria:
Contraindication for study drugs
Pre-existing antibiotic therapy within 14 days of surgery
Any doubt that patients can make the decision to participate fully informed due to cognitive impairment, such as in critically ill or demented patients.
Emergency procedures with planned incision within 2 hours after the surgeon indicated the procedure
Participation in other studies that could potentially interfere with the present one (according to the ethics committee)
Combined surgery including surgical subspecialties other than the above mentioned
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter P. Weber, MD
Organizational Affiliation
University Hospital Basel, Basel 4031 Basel, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Basel
City
Basel
State/Province
Baselstadt
ZIP/Postal Code
4031
Country
Switzerland
12. IPD Sharing Statement
Citations:
PubMed Identifier
34750659
Citation
Kopp Lugli A, Marti WR, Salm L, Mujagic E, Bundi M, von Strauss M, Bucheli Laffer E, Landin J, Fux CA, Coslovsky M, Weber WP, Kindler C. The Role of HbA1c as a Positive Perioperative Predictor of Surgical Site and Other Postoperative Infections: An Explorative Analysis in Patients Undergoing Minor to Major Surgery. World J Surg. 2022 Feb;46(2):391-399. doi: 10.1007/s00268-021-06368-x. Epub 2021 Nov 8. Erratum In: World J Surg. 2021 Nov 24;:
Results Reference
derived
PubMed Identifier
28385346
Citation
Weber WP, Mujagic E, Zwahlen M, Bundi M, Hoffmann H, Soysal SD, Kraljevic M, Delko T, von Strauss M, Iselin L, Da Silva RXS, Zeindler J, Rosenthal R, Misteli H, Kindler C, Muller P, Saccilotto R, Lugli AK, Kaufmann M, Gurke L, von Holzen U, Oertli D, Bucheli-Laffer E, Landin J, Widmer AF, Fux CA, Marti WR. Timing of surgical antimicrobial prophylaxis: a phase 3 randomised controlled trial. Lancet Infect Dis. 2017 Jun;17(6):605-614. doi: 10.1016/S1473-3099(17)30176-7. Epub 2017 Apr 3. Erratum In: Lancet Infect Dis. 2017 Dec;17 (12 ):1232.
Results Reference
derived
PubMed Identifier
24885132
Citation
Mujagic E, Zwimpfer T, Marti WR, Zwahlen M, Hoffmann H, Kindler C, Fux C, Misteli H, Iselin L, Lugli AK, Nebiker CA, von Holzen U, Vinzens F, von Strauss M, Reck S, Kraljevic M, Widmer AF, Oertli D, Rosenthal R, Weber WP. Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial. Trials. 2014 May 24;15:188. doi: 10.1186/1745-6215-15-188.
Results Reference
derived
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Randomized Controlled Trial to Evaluate the Optimal Timing of Surgical Antimicrobial Prophylaxis
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