Clinical trial NCT05499481: Short Against Long Antibiotic Therapy for Infected Orthopedic Sites
Official title: Short Against Long Antibiotic Therapy for Infected Orthopedic Sites
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Orthopedic Devices Associated With Misadventures
Infection, Surgical Site
Antibiotic Side Effect
Keywords: Orthopedic infectionsT
Duration
Antibiotic Therapy
Randomized-Controlled Trial
Lead sponsor: Balgrist University Hospital
Sponsor class: OTHER
First posted: 2022-08-12
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Clinical remission related to the duration of total, postdebridement, antibiotic use
timeFrame: 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
measure: Microbiological recurrence in relation to the total, postdebridement, antibiotic use
timeFrame: 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary outcomes:
measure: Description of all clinical failures of any sort
timeFrame: 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
measure: Adverse events in each study arm, and in relation to the antibiotics used
timeFrame: 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
measure: Length of hospital stay in acute care surgery (without rehabilitation)
timeFrame: 6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Other outcomes:
Locations:
city: Zurich
country: Switzerland
facility: Balgrist University Hospital
Study officials:
affiliation: Balgrist University Hospital
name: Ilker Uçkay, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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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.
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.
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.
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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.
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