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Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery (BAPTIST)

Primary Purpose

Surgical Site Infection, Microbial Colonization, Antibiotic Resistant Infection

Status
Recruiting
Phase
Phase 3
Locations
Switzerland
Study Type
Interventional
Intervention
Standard antibiotic prophylaxis
Sponsored by
Balgrist University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Surgical Site Infection focused on measuring Perioperative antibiotic prophylaxis, Selection, High Risk patients, Ranndomized-Controlled Trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • Age ≥ 18 years
  • Surgery under current or recent therapeutic antibiotics (antibiotic-free window <14 days and past antibiotic prescription >4 days)
  • Surgery for open fractures and wounds; including 2nd and 3rd looks
  • Potentially contaminated wound revision in the operating theatre
  • Tumor (oncologic) surgery (if prior radiotherapy and/or bone involvement)
  • Spine surgery with ASA-Score >= 3 points, sacral involvement, or re-vision surgery
  • Known skin colonization with multidrug-resistant Gram-negative bacteria

Exclusion Criteria:

  • Inability to understand the study procedure for linguistic or cognitive rea-sons
  • Surgery without intraoperative microbiological samples
  • Allergy or major intolerance to vancomycin and/or gentamicin
  • Anticipated clinical follow-up of less than 6 weeks after inclusion
  • Pregnant or breastfeeding women
  • Known carriage of multiresistant Gram-negative bacteria in the urine or anal region

Sites / Locations

  • Balgrist University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard prophylaxis arm

Innovative prophylaxis arm

Arm Description

The standard prophylaxis consists of one to three intravenous doses of cefuroxime 1.5 g intravenously; or cefuroxim 3g if obesity > 120 kg or a BMI > 35 kg/m2; or vancomycin 1 g or clindamycin 600 mg in case of intolerance to cephalosporins In patients alrady under current therapuetic antibiotic therapy, continuation of that therapuetic antibiotic regimen

Additional single-shot perioperative antibiotic prophylaxis with Broad-spectrum prophylaxis: vancomycin 1 g & gentamicin 5 mg/kg.

Outcomes

Primary Outcome Measures

Incidence of Surgical Site Infections (SSI) at 6 weeks for surgeries without implant; and 1 year for surgeries with implant
Assessment of SSI at the clinical controls according to clinical criteria in the literature (pus, discharge, pain, inflammation, several deep tissue microbiological cultures

Secondary Outcome Measures

Proportion of antibiotic-resistant pathogens in the deep surgical site of the study patients; in relation to the prior antibiotic prophylaxis or the current therapeu-tic antibiotic therapy
Assessments of antibiotic resistance of pathogens according to standard susceptibilty testing in the Microbiological Laboratory
Incidence of revision surgery for non-infections reasons within 6 weeks
Unplanned revision surgery in the operating theatre for any reasons
Proportion of the change of antibiotic therapy based on intraoperative findings
Asssesment in the medical files. Have therapeutic antibiotics been changed according to new intraoperative bacterial culture findings
Incidence of dverse events and global costs of therapeutic antibiotics (if any)
If there is therapeutic antibiotc treatment necessary, the investigators assess the drugs, the adverse events and the global costs related to the antibiotc treatment. The costs are the global (overall) hospitalizations costs in Swiss Francs.
Incidence of non-SSI infections within 6 weeks (e.g. urine infections)
Assessment of all nosocomial and community-acquired infections ocrruging in the immediate postoperative period and relate them to prior perioperative antibiotic prophylaxis
Incidence of skin and body colonization with Gram-negative multi-resistant bacteriaweeks (if there are any samples)
Assessment of the impact of the priorantibiotic prophylaxis on the body colonization with multiresistant bacteria of concern for infection control

Full Information

First Posted
August 11, 2022
Last Updated
February 27, 2023
Sponsor
Balgrist University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05502380
Brief Title
Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery
Acronym
BAPTIST
Official Title
Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Sur-gery - the Prospective-randomized, Microbiologist-blinded, Stratified, Superiority Trials - BAPTIST Trials
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 15, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Balgrist University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The perioperative antibiotic prophylaxis is evidence-based in orthopedic surgery. While its duration ranges from a single dose to three doses throughout the world, the choice of the prophylactic agents is undisputed. Worldwide, the surgeons use 1st or 2nd-generation cephalosporins (or vancomycin in some cases). However, there are particular clinical situation with a high risk of antibiotic-resistant surgical site infections (SSI); independently of the duration of adminis-tered prophylaxis. These resistant SSI's occur in contaminated wounds, or during surgery under current therapeutic antibiotics, and base on "selection" by antibiotics used for therapy or for prophylaxis.
Detailed Description
The perioperative antibiotic prophylaxis is evidence-based for the majority of orthopedic surgeries. While the debate of its duration and timing (single-dose versus triple-dose; before or after the intraoperative microbiological sampling) may continue, no clinicians doubt on the efficiency of the recommended prophylactic agents; that are mostly 1st or 2nd-generation cephalosporins, co-amoxiclav or other exceptional agents in cases of (pseudo)-allergy. However. and traditionally, up to the half of all detected pathogens of orthopedic SSI's are not covered by the prior prophylactic regimens: e.g. SSIs due to methicillin-resistant cocci or non-fermenting Gram-negative rods in orthopedic surgery. Additionally, orthopedic surgeons operating selected patient populations (neoplasms, open fractures, postoperative wound dehiscence9, diabetic foot infections or already infected body sites) experience a high risk of prophylactic-resistant pathogens, or pathogens resistant to current therapeutic antibiotics regimens. At least 10% of all new intraoperative tissue samples, during iterative surgical debridement, yield (new) pathogens unknown to the clinicians. This is due to selection by prophylactic or therapeutic antibiotics, which only kill the previously detected pathogens, but left over newly introduced contaminants, remnant parts of partially-diagnosed polymicrobial infections; ultimately leading to a new SSIs occurring during therapy for the first infection at the orthopedic site. This selection is unpredictable involving both Gram-positive skin pathogens as well as (multi) resistant Gram-negative rods.From a microbiological point of view, only a maximal Gram-negative coverage, alongside with a large Gram-negative coverage, would cover these selections. The literature is in-existing how to prevent these selections. Most clinicians just continue with the standard prophylactic recommendation, or the current thera-peutic antibiotic regimen. Theoretically, clinicians cannot exclude that these selected patient populations eventually might profit from a broad-spectrum prophylaxis. The BAPTIST trials only concern the perioperative antibiotic prophylaxis in selected situations of orthopedic surgery: tumor surgery, debridement for postoperative dehiscent wounds, debridement under antibiotics, open fractures, skin colonization with multidrug-resistant bacteria, plus, as a control; spine surgery in selected multimorbid patients. The investigators alternately randomize the standard prophylaxis (or by continuing the current antibiotic treatment) to the additional broad-spectrum single-shot of vancomycin 1g IV & single-shot of gentamicin 5 mg/kg intravenously; before an eventual intraoperative sampling. End-of-Treatment (EOT) and/or Test-of-Cure (TOC) occur latest at the 6-week's surgical control visit. The rest of the hospital stay, treatment, the use of negative-pressure vacuum therapy, other interventions, local antibiotic therapies; therapies or procedure are at the discretion of the treating clinicians. The investogators will randomize surgical interventions defined by the inclusion criteria in a prospective-alternating scheme (1:1) according to the scheduled position in the operating theatres. The anesthetists (or the nurses at the hospitalization units) the will administer the standard prophylaxis (or the therapeutic antibiotics) alone, or with the addition of the single-shot broad-spectrum prophylaxis regimen composed of vancomycin and gentamicin. In case of clinical suspicion of infection or massive contamination, the surgeons will perform at least three microbiological intraoperative tissue samples. Each surgery counts as an independent event. If a patient is debrided several times, he/she can have different prophylaxis regimens during each of the interventions. After the prophylactic regimen, the clinicians are free to continue with a targeted or empirical therapeutic antibiotic regimen. The antibiotic therapy per se is not an objective of this current trials. The treatment period includes the following daily study visits: Visit 1 - Enrollment (Day 1) EOT (end of microbiological cultures) - Day 14 (+/- 3 days) TOC (clinical surgical control) - Day 42 (+/- 14 days) Follow-up (telephone) for implant-related surgery - 1 year (+/- 2 months)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Surgical Site Infection, Microbial Colonization, Antibiotic Resistant Infection
Keywords
Perioperative antibiotic prophylaxis, Selection, High Risk patients, Ranndomized-Controlled Trial

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
At enrollment (Day 1), the investigator will prescribe the preoperative antibiotic prophylaxis based on instructions provided in the protocol according to the patient's randomization. Patients will be randomized in the ratio 1:1 into the investigational group (broad-spectrum prophylaxis) and the control group (usual prophylaxis). Each patient can be included several times with one episode for each surgical interven-tion in the operating theatre. The initial consent form is valid during 1 month and will be renewed in case of another inclusion following a delay of 1 month after the initial signature of the patient.
Masking
Care Provider
Masking Description
The microbiologists culturing the pathogens of eventual surgical site infections are blinded to the prior prophylaxis during the index surgery
Allocation
Randomized
Enrollment
414 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard prophylaxis arm
Arm Type
Active Comparator
Arm Description
The standard prophylaxis consists of one to three intravenous doses of cefuroxime 1.5 g intravenously; or cefuroxim 3g if obesity > 120 kg or a BMI > 35 kg/m2; or vancomycin 1 g or clindamycin 600 mg in case of intolerance to cephalosporins In patients alrady under current therapuetic antibiotic therapy, continuation of that therapuetic antibiotic regimen
Arm Title
Innovative prophylaxis arm
Arm Type
Experimental
Arm Description
Additional single-shot perioperative antibiotic prophylaxis with Broad-spectrum prophylaxis: vancomycin 1 g & gentamicin 5 mg/kg.
Intervention Type
Drug
Intervention Name(s)
Standard antibiotic prophylaxis
Intervention Description
One to three intravenous doses of cefuroxime 1.5 g intravenously; or 3g if obesity; or vancomycin 1 g or clindamycin 600 mg; if allergy. Continuation of eventual current therapeutic antibiotc regimens for any infection
Primary Outcome Measure Information:
Title
Incidence of Surgical Site Infections (SSI) at 6 weeks for surgeries without implant; and 1 year for surgeries with implant
Description
Assessment of SSI at the clinical controls according to clinical criteria in the literature (pus, discharge, pain, inflammation, several deep tissue microbiological cultures
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary Outcome Measure Information:
Title
Proportion of antibiotic-resistant pathogens in the deep surgical site of the study patients; in relation to the prior antibiotic prophylaxis or the current therapeu-tic antibiotic therapy
Description
Assessments of antibiotic resistance of pathogens according to standard susceptibilty testing in the Microbiological Laboratory
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Title
Incidence of revision surgery for non-infections reasons within 6 weeks
Description
Unplanned revision surgery in the operating theatre for any reasons
Time Frame
6 weeks postoperatively
Title
Proportion of the change of antibiotic therapy based on intraoperative findings
Description
Asssesment in the medical files. Have therapeutic antibiotics been changed according to new intraoperative bacterial culture findings
Time Frame
6 weeks postoperatively
Title
Incidence of dverse events and global costs of therapeutic antibiotics (if any)
Description
If there is therapeutic antibiotc treatment necessary, the investigators assess the drugs, the adverse events and the global costs related to the antibiotc treatment. The costs are the global (overall) hospitalizations costs in Swiss Francs.
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Title
Incidence of non-SSI infections within 6 weeks (e.g. urine infections)
Description
Assessment of all nosocomial and community-acquired infections ocrruging in the immediate postoperative period and relate them to prior perioperative antibiotic prophylaxis
Time Frame
6 weeks postoperatively
Title
Incidence of skin and body colonization with Gram-negative multi-resistant bacteriaweeks (if there are any samples)
Description
Assessment of the impact of the priorantibiotic prophylaxis on the body colonization with multiresistant bacteria of concern for infection control
Time Frame
4-6 weeks postoperatively

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Age ≥ 18 years Surgery under current or recent therapeutic antibiotics (antibiotic-free window <14 days and past antibiotic prescription >4 days) Surgery for open fractures and wounds; including 2nd and 3rd looks Potentially contaminated wound revision in the operating theatre Tumor (oncologic) surgery (if prior radiotherapy and/or bone involvement) Spine surgery with ASA-Score >= 3 points, sacral involvement, or re-vision surgery Known skin colonization with multidrug-resistant Gram-negative bacteria Exclusion Criteria: Inability to understand the study procedure for linguistic or cognitive rea-sons Surgery without intraoperative microbiological samples Allergy or major intolerance to vancomycin and/or gentamicin Anticipated clinical follow-up of less than 6 weeks after inclusion Pregnant or breastfeeding women Known carriage of multiresistant Gram-negative bacteria in the urine or anal region
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ilker Uçkay, Professor
Phone
++41 44 386 37 05
Email
ilker.uckay@balgrist.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Mazda Farshad, Professor
Phone
++ 41 44 386 30 00
Email
mazda.farshad@balgrist.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ilker Uçkay, Professor
Organizational Affiliation
Balgrist University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Balgrist University Hospital
City
Zurich
ZIP/Postal Code
8008
Country
Switzerland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The investigators might share anonomyzed key elements (data) upon scientific request to the corresponding person
IPD Sharing Time Frame
After the intermi analyses
IPD Sharing Access Criteria
The ivestigators might bilaterally share anonomyzed key elements (data) upon scientific request to the corresponding person
Citations:
PubMed Identifier
23414705
Citation
Uckay I, Hoffmeyer P, Lew D, Pittet D. Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update. J Hosp Infect. 2013 May;84(1):5-12. doi: 10.1016/j.jhin.2012.12.014. Epub 2013 Feb 14.
Results Reference
background
PubMed Identifier
31851708
Citation
Wuarin L, Abbas M, Harbarth S, Waibel F, Holy D, Burkhard J, Uckay I. Changing perioperative prophylaxis during antibiotic therapy and iterative debridement for orthopedic infections? PLoS One. 2019 Dec 18;14(12):e0226674. doi: 10.1371/journal.pone.0226674. eCollection 2019.
Results Reference
background
PubMed Identifier
28529866
Citation
Jamei O, Gjoni S, Zenelaj B, Kressmann B, Belaieff W, Hannouche D, Uckay I. Which Orthopaedic Patients Are Infected with Gram-negative Non-fermenting Rods? J Bone Jt Infect. 2017 Jan 15;2(2):73-76. doi: 10.7150/jbji.17171. eCollection 2017.
Results Reference
background
PubMed Identifier
31966954
Citation
Muller D, Kaiser D, Sairanen K, Studhalter T, Uckay I. Antimicrobial Prophylaxis for the Prevention of Surgical Site Infections in Orthopaedic Oncology - A Narrative Review of Current Concepts. J Bone Jt Infect. 2019 Oct 15;4(6):254-263. doi: 10.7150/jbji.39050. eCollection 2019.
Results Reference
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Broad-spectrum Antibiotic Prophylaxis in Tumor and Infected Orthopedic Surgery

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