Short Against Long Antibiotic Therapy for Infected Orthopedic Sites

NCT05499481 | Completed Phase 3 DMC

• 1 other identifier: BASEC 2022-01012
• Study Type: interventional
• Target: 495
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Orthopedic infectionsT; Duration; Antibiotic Therapy; Randomized-Controlled Trial

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Description of all clinical failures of any sort

  6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery

• Adverse events in each study arm, and in relation to the antibiotics used

  6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery

• Length of hospital stay in acute care surgery (without rehabilitation)

  6 weeks postoperatively, or 1 year postoperatively in case of implant-related orthopedic surgery

Study Arms (2)

Long Antibiotic Arm

ACTIVE COMPARATOR

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

Drug: Antibiotic

Short Antibiotic Arm

EXPERIMENTAL

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

Drug: Antibiotic

Interventions

Antibiotic DRUG

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.

Long Antibiotic Arm; Short Antibiotic Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Balgrist University Hospital: lead

Study Sites (1)

Balgrist University Hospital

Zurich, 8008, Switzerland

Location

Related Publications (14)

• 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.

  PMID: 28804007 BACKGROUND

• 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.

  PMID: 20540962 BACKGROUND

• 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.

  PMID: 30744128 BACKGROUND

• 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.

  PMID: 20012334 BACKGROUND

• 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.

  PMID: 33242083 BACKGROUND

• 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.

  PMID: 31915048 BACKGROUND

• 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.

  PMID: 31106353 BACKGROUND

• 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.

  PMID: 21318568 BACKGROUND

• 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.

  PMID: 32028985 BACKGROUND

• 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.

  PMID: 30348550 BACKGROUND

• 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.

  PMID: 27524103 BACKGROUND

• 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.

  PMID: 34042388 BACKGROUND

• Zendeli F, Jedrusik A, Schaefer RO, Albrecht D, Betz M, Waibel FWA, Grober T, Kuhne N, Konneker S, Uckay I. Pathogen-Specific Risk for Iterative Surgical Debridement in Orthopedic Infections: A Prospective Multicohort Analysis. J Clin Med. 2025 Dec 10;14(24):8750. doi: 10.3390/jcm14248750.

  PMID: 41464652 DERIVED

• Uckay I, Wirth S, Zorner B, Fucentese S, Wieser K, Schweizer A, Muller D, Zingg P, Farshad M. Study protocol: short against long antibiotic therapy for infected orthopedic sites - the randomized-controlled SALATIO trials. Trials. 2023 Feb 18;24(1):117. doi: 10.1186/s13063-023-07141-2.

  PMID: 36803837 DERIVED

MeSH Terms

Conditions

Surgical Wound Infection

Interventions

Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Ilker Uçkay, Professor

  Balgrist University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 12, 2022
• Study Start: September 15, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: after the first interim analysis
• Access Criteria: The investigators might share anonymized key elements upon reasonable scientific request to the corresponding persons

Locations

CH (1)