Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

Antibiotic Side Effect Clinical Trial

— SALATIO  

Official title:

Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05499481
• Other study ID #: BASEC 2022-01012
• Status: Recruiting
• Phase: Phase 3
• Start date: September 15, 2022
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2023
• Source: Balgrist University Hospital
• Contact: Ilker Uçkay, Professor
• Phone: ++41 44 386 37 05
• Email: ilker.uckay[@]balgrist.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: September 30, 2025
• Est. primary completion date: September 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Antibiotic
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.

Locations

Country	Name	City	State
Switzerland	Balgrist University Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Balgrist University Hospital

Country where clinical trial is conducted

Switzerland, 

References & Publications (12)

Argenson JN, Arndt M, Babis G, Battenberg A, Budhiparama N, Catani F, Chen F, de Beaubien B, Ebied A, Esposito S, Ferry C, Flores H, Giorgini A, Hansen E, Hernugrahanto KD, Hyonmin C, Kim TK, Koh IJ, Komnos G, Lausmann C, Loloi J, Lora-Tamayo J, Lumban-Gaol I, Mahyudin F, Mancheno-Losa M, Marculescu C, Marei S, Martin KE, Meshram P, Paprosky WG, Poultsides L, Saxena A, Schwechter E, Shah J, Shohat N, Sierra RJ, Soriano A, Stefansdottir A, Suleiman LI, Taylor A, Triantafyllopoulos GK, Utomo DN, Warren D, Whiteside L, Wouthuyzen-Bakker M, Yombi J, Zmistowski B. Hip and Knee Section, Treatment, Debridement and Retention of Implant: Proceedings of International Consensus on Orthopedic Infections. J Arthroplasty. 2019 Feb;34(2S):S399-S419. doi: 10.1016/j.arth.2018.09.025. Epub 2018 Oct 19. No abstract available. — View 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. — View Citation

Bernard L, Arvieux C, Brunschweiler B, Touchais S, Ansart S, Bru JP, Oziol E, Boeri C, Gras G, Druon J, Rosset P, Senneville E, Bentayeb H, Bouhour D, Le Moal G, Michon J, Aumaitre H, Forestier E, Laffosse JM, Begue T, Chirouze C, Dauchy FA, Devaud E, Martha B, Burgot D, Boutoille D, Stindel E, Dinh A, Bemer P, Giraudeau B, Issartel B, Caille A. Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection. N Engl J Med. 2021 May 27;384(21):1991-2001. doi: 10.1056/NEJMoa2020198. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Lora-Tamayo J, Euba G, Cobo J, Horcajada JP, Soriano A, Sandoval E, Pigrau C, Benito N, Falgueras L, Palomino J, Del Toro MD, Jover-Saenz A, Iribarren JA, Sanchez-Somolinos M, Ramos A, Fernandez-Sampedro M, Riera M, Baraia-Etxaburu JM, Ariza J; Prosthetic Joint Infection Group of the Spanish Network for Research in Infectious Diseases-REIPI. Short- versus long-duration levofloxacin plus rifampicin for acute staphylococcal prosthetic joint infection managed with implant retention: a randomised clinical trial. Int J Antimicrob Agents. 2016 Sep;48(3):310-6. doi: 10.1016/j.ijantimicag.2016.05.021. Epub 2016 Aug 3. — View 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. — View 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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Primary	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	6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary	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)	6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary	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.	6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery
Secondary	Length of hospital stay in acute care surgery (without rehabilitation)	The duration of the hospital stay for every episode in both randomizing arm	6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery