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Short Against Long Antibiotic Therapy for Infected Orthopedic Sites (SALATIO)

Primary Purpose

Orthopedic Devices Associated With Misadventures, Infection, Surgical Site, Antibiotic Side Effect

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

About this trial

This is an interventional treatment trial for Orthopedic Devices Associated With Misadventures focused on measuring Orthopedic infectionsT, Duration, Antibiotic Therapy, Randomized-Controlled Trial

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥ 18 years on admission
  • Orthopedic bone and implant infections including musculoskeletal grafts
  • Intraoperative debridement with any surgical technique
  • 12 months of scheduled follow-up from hospitalization
  • Bacterial orthopedic infections of any nature
  • First or second episode of infection

Exclusion Criteria:

  • Mycobacterial, fungal, nocardial, and Actinomyces infections
  • Purely soft tissue infections
  • Non-resected cancer in the infection site
  • Purely intrasynovial infections (native joint septic arthritis)
  • More than three debridements performed for infection
  • Absence of at least one surgical intraoperative debridement
  • Spine infections (investigated in another trial)10
  • Diabetic foot infections (investigated in another trial)7
  • Documented endocarditis according to the Duke criteria
  • At least 2 prior infection episodes at the actual infection site

Sites / Locations

  • Balgrist University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Long Antibiotic Arm

Short Antibiotic Arm

Arm Description

Without implant material in place: 6 weeks of systemic post-surgical antibiotic therapy With mateial in place 12 weeks of systemic post-surgical antibiotic therapy

Without implant material in place: 3 weeks of systemic post-surgical antibiotic therapy With mateial in place 6 weeks of systemic post-surgical antibiotic therapy

Outcomes

Primary Outcome Measures

Clinical remission related to the duration of total, postdebridement, antibiotic use
Clinical assessment during routine surgical controls. Definition of clinical failure accoding to to sandard criteria in the literature (surgical revision, pain, local inflammation, discharge, several deep intraoperative bacterial tissue samples)
Microbiological recurrence in relation to the total, postdebridement, antibiotic use
Recurrence of infection, with the same pathogens, after completing the antibiotic treatment for the index infection

Secondary Outcome Measures

Description of all clinical failures of any sort
Need for hospitalisation or revision surgery for any non-infectious failures related to the operation wound (hematoma, seroma, internal (closed) fractures, dislocation of implants)
Adverse events in each study arm, and in relation to the antibiotics used
All adverse events during the therapy and follow-up time , with an emphasis on antibiotic-related adverse events (according to medical judgement). Numbers and descriptions.
Length of hospital stay in acute care surgery (without rehabilitation)
The duration of the hospital stay for every episode in both randomizing arm

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
NCT05499481
Brief Title
Short Against Long Antibiotic Therapy for Infected Orthopedic Sites
Acronym
SALATIO
Official Title
Short Against Long Antibiotic Therapy for Infected Orthopedic Sites
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
September 15, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (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 investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.
Detailed Description
The optimal duration of postoperative, systemic antibiotic therapy for implant-related orthopedic infections, with or without implant removal, is unknown. Retrospective studies suggest that a maximum duration of 6 weeks is not inferior to longer administrations; even if the infected implants are kept in place or during a one-stage exchange. Prospective-randomized trials (RCT) suggest that even shorter durations, such 3 or 4 weeks, are possible, when the implant is removed. Likewise, in prospective studies, 6 or 8 weeks of systemic antibiotics are not inferior to the current 12 weeks during DAIR (debridement, antibiotic and implant retention), or during the one-stage exchange; except for one single RCT suggesting a better outcome for 12 weeks in the substrata of arthroplasty infections undergoing the DAIR procedure. However, these RCTs concern selected branches of orthopedic surgery; especially prosthetic joint infections. The investigators intend to expand these evaluations to all fields of orthopedic and hand surgery. The only exceptions would be spine surgery, for which a multicenter, separate RCT is already under way (SASI-trials). The second exception would be the treatment of implant-free diabetic foot infections, for which two RCTs are underway.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Orthopedic Devices Associated With Misadventures, Infection, Surgical Site, Antibiotic Side Effect
Keywords
Orthopedic infectionsT, Duration, Antibiotic Therapy, Randomized-Controlled Trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Long Antibiotic Arm
Arm Type
Active Comparator
Arm Description
Without implant material in place: 6 weeks of systemic post-surgical antibiotic therapy With mateial in place 12 weeks of systemic post-surgical antibiotic therapy
Arm Title
Short Antibiotic Arm
Arm Type
Experimental
Arm Description
Without implant material in place: 3 weeks of systemic post-surgical antibiotic therapy With mateial in place 6 weeks of systemic post-surgical antibiotic therapy
Intervention Type
Drug
Intervention Name(s)
Antibiotic
Intervention Description
The investigators will perform two concomitant RCTs, depending on the presence of infected osteosynthesis material at enrolment: - SALATIO 1. Infected implant not removed (or new material inserted): Randomization 6 vs. 12 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy. - SALATIO 2. Infected implant without residual material (definitive removal or within the interval of a two-stage exchange): Randomization 3 vs. 6 weeks (+/- 5 days) of total antibiotic therapy counted since the first debridement for infection. Early switch to oral targeted therapy.
Primary Outcome Measure Information:
Title
Clinical remission related to the duration of total, postdebridement, antibiotic use
Description
Clinical assessment during routine surgical controls. Definition of clinical failure accoding to to sandard criteria in the literature (surgical revision, pain, local inflammation, discharge, several deep intraoperative bacterial tissue samples)
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Title
Microbiological recurrence in relation to the total, postdebridement, antibiotic use
Description
Recurrence of infection, with the same pathogens, after completing the antibiotic treatment for the index infection
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary Outcome Measure Information:
Title
Description of all clinical failures of any sort
Description
Need for hospitalisation or revision surgery for any non-infectious failures related to the operation wound (hematoma, seroma, internal (closed) fractures, dislocation of implants)
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Title
Adverse events in each study arm, and in relation to the antibiotics used
Description
All adverse events during the therapy and follow-up time , with an emphasis on antibiotic-related adverse events (according to medical judgement). Numbers and descriptions.
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Title
Length of hospital stay in acute care surgery (without rehabilitation)
Description
The duration of the hospital stay for every episode in both randomizing arm
Time Frame
6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years on admission Orthopedic bone and implant infections including musculoskeletal grafts Intraoperative debridement with any surgical technique 12 months of scheduled follow-up from hospitalization Bacterial orthopedic infections of any nature First or second episode of infection Exclusion Criteria: Mycobacterial, fungal, nocardial, and Actinomyces infections Purely soft tissue infections Non-resected cancer in the infection site Purely intrasynovial infections (native joint septic arthritis) More than three debridements performed for infection Absence of at least one surgical intraoperative debridement Spine infections (investigated in another trial)10 Diabetic foot infections (investigated in another trial)7 Documented endocarditis according to the Duke criteria At least 2 prior infection episodes at the actual infection site
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 anonymized key elements upon reasonable scientific request to the corresponding persons
IPD Sharing Time Frame
after the first interim analysis
IPD Sharing Access Criteria
The investigators might share anonymized key elements upon reasonable scientific request to the corresponding persons
Citations:
PubMed Identifier
28804007
Citation
Chaussade H, Uckay I, Vuagnat A, Druon J, Gras G, Rosset P, Lipsky BA, Bernard L. Antibiotic therapy duration for prosthetic joint infections treated by Debridement and Implant Retention (DAIR): Similar long-term remission for 6 weeks as compared to 12 weeks. Int J Infect Dis. 2017 Oct;63:37-42. doi: 10.1016/j.ijid.2017.08.002. Epub 2017 Aug 10.
Results Reference
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PubMed Identifier
20540962
Citation
Bernard L, Legout L, Zurcher-Pfund L, Stern R, Rohner P, Peter R, Assal M, Lew D, Hoffmeyer P, Uckay I. Six weeks of antibiotic treatment is sufficient following surgery for septic arthroplasty. J Infect. 2010 Jul;61(2):125-32. doi: 10.1016/j.jinf.2010.05.005. Epub 2010 Jun 9.
Results Reference
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PubMed Identifier
30744128
Citation
Hirsiger S, Betz M, Stafylakis D, Gotschi T, Lew D, Uckay I. The Benefice of Mobile Parts' Exchange in the Management of Infected Total Joint Arthroplasties with Prosthesis Retention (DAIR Procedure). J Clin Med. 2019 Feb 9;8(2):226. doi: 10.3390/jcm8020226.
Results Reference
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PubMed Identifier
20012334
Citation
Farhad R, Roger PM, Albert C, Pelligri C, Touati C, Dellamonica P, Trojani C, Boileau P. Six weeks antibiotic therapy for all bone infections: results of a cohort study. Eur J Clin Microbiol Infect Dis. 2010 Feb;29(2):217-22. doi: 10.1007/s10096-009-0842-1. Epub 2009 Dec 10.
Results Reference
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PubMed Identifier
33242083
Citation
Gariani K, Pham TT, Kressmann B, Jornayvaz FR, Gastaldi G, Stafylakis D, Philippe J, Lipsky BA, Uckay L. Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial. Clin Infect Dis. 2021 Oct 5;73(7):e1539-e1545. doi: 10.1093/cid/ciaa1758.
Results Reference
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PubMed Identifier
31915048
Citation
Waibel F, Berli M, Catanzaro S, Sairanen K, Schoni M, Boni T, Burkhard J, Holy D, Huber T, Bertram M, Laubli K, Frustaci D, Rosskopf A, Botter S, Uckay I. Optimization of the antibiotic management of diabetic foot infections: protocol for two randomized controlled trials. Trials. 2020 Jan 8;21(1):54. doi: 10.1186/s13063-019-4006-z.
Results Reference
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PubMed Identifier
31106353
Citation
Benkabouche M, Racloz G, Spechbach H, Lipsky BA, Gaspoz JM, Uckay I. Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial. J Antimicrob Chemother. 2019 Aug 1;74(8):2394-2399. doi: 10.1093/jac/dkz202.
Results Reference
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PubMed Identifier
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Citation
Rod-Fleury T, Dunkel N, Assal M, Rohner P, Tahintzi P, Bernard L, Hoffmeyer P, Lew D, Uckay I. Duration of post-surgical antibiotic therapy for adult chronic osteomyelitis: a single-centre experience. Int Orthop. 2011 Nov;35(11):1725-31. doi: 10.1007/s00264-011-1221-y. Epub 2011 Feb 12.
Results Reference
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PubMed Identifier
32028985
Citation
Betz M, Uckay I, Schupbach R, Grober T, Botter SM, Burkhard J, Holy D, Achermann Y, Farshad M. Short postsurgical antibiotic therapy for spinal infections: protocol of prospective, randomized, unblinded, noninferiority trials (SASI trials). Trials. 2020 Feb 6;21(1):144. doi: 10.1186/s13063-020-4047-3.
Results Reference
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PubMed Identifier
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Citation
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PubMed Identifier
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Citation
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Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

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