Clinical trial NCT01816009: Treatment of the Infections on Osteo-articular Prostheses by 6 Versus 12 Weeks of Antibiotherapy
Official title: Multicentric Study, of Non Inferiority, Randomized, Opened, to Evaluate the Two Durations Effectiveness of Antibiotherapy (6 Weeks Versus 12 Weeks) in the Treatment of Osteo-articular Prostheses Infections, With Prosthetic Change (in 1 Time or 2 Long Times) or Not (Articular Washing)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prosthesis-related Infections
Keywords: infection
antibiotic
prosthesis
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2013-03-21
Enrollment: 410
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a prospective, open randomized, non-inferiority trial with two parallel groups, comparing 6 weeks versus 12 weeks of antibiotic treatment following surgery procedure (debridement and retention, 1-stage or 2 stage exchange).

The duration of the treatment antibiotic of prosthetic joint infections is only based on experts' opinion ; this one varies from 6 weeks to several months according to the customs of the influencer.

The principal aim of this study is to explore the efficacy and safety of 6 weeks versus 12 weeks antibiotic therapy duration, both associated with surgical procedure (debridement and retention of implant, one-stage or two stages exchange), in PJI treatment.

The study concerns 410 men or women of more than 18 years include in 34 centres in France.

The duration of the study is of 4 years.

Detailed description: Although the infection risk following primary hip and knee arthroplasties is less than 2%, prosthetic joint infections (PJI) have become more frequent due to the increasing number of patients undergoing surgery. PJI remains one of the most serious complications of prosthetic joint implantation. Each PJI episode represents substantial morbidity with a 5.3-7.2-fold higher cost than for the initial arthroplasty. The management of PJI almost always necessitates the need for surgical intervention and prolonged courses of intravenous or oral antimicrobial therapy. Despite a significant amount of basic and clinical research in this field, many questions pertaining to the definition of infection as well as diagnosis and management of these infections remain unanswered. The optimal surgical and antibiotic treatment of PJI remains unclear. The infection of implant is difficult to treat. According to the Infectious Diseases Society America recommendations of Osmon et al. in 2012, antibiotic therapy duration varies: 3 months for hip arthroplasties (6 months for total knee arthroplasties) for PJI with arthroplasty retention, and 6 weeks for two-stage exchanges.

Sometimes, excessive antibiotic treatment durations are performed because recommendations are not evidence-based sensu strictu and only based on experts' opinion. Short therapy should be benefit to ecologic and economic impact.

While the usual treatment is by the parenteral route for the first 2-4 weeks, this attitude is not evidence-based either. Up to one-third of patients with PJI may experience antibiotic-related or catheter-related problems during parenteral treatment. The one-stage and two-stage exchange of the infected implant has rather comparable success rate in the surgical management of the PJI (about 90%). Recent no-randomized studies indicate that short antibiotic therapy (6 weeks) seems to be efficient.

Our proposal study is to explore the efficacy and safety of 6 weeks in the treatment of PJI, after a surgical procedure.

The principal aim of this study is to explore the efficacy and safety of 6 weeks versus 12 weeks antibiotic therapy duration, both associated with surgical procedure (debridement and retention of implant, one-stage or two stages exchange), in PJI treatment.

Treatments antibiotics are chosen according to the germ and according to the consensual recommendations. Used antibiotics already have the AMM in this indication.

Eligible patients have at least one symptom relating to the PJI (such pain, sinus tract, inflammatory surgical scar...) and microbiological documentation of PJI.The primary endpoint is the occurrence of clinical cure at month 24. Secondary endpoints are (i) adequate clinical and biological response at months 6 and 12, (ii) incidence of adverse events in the two groups, (iii) oral and/or intravenous antibiotic therapy efficacy.

Randomization is stratified by the anatomical location of the infected joint (hip or knee) and surgical procedure (debridement and retention, 1-stage or 2 stage exchange).

The follow-up consists on periodic clinical examinations, anamnesis and occasionally laboratory or radiological controls.

Eligibility criteria: Inclusion Criteria:

* Men or women over 18, presenting at least one of the following clinical signs: pain, fever, dent or flow of scar
* Bacterial infection on osteo-articular prosthesis (hip or knee)
* Documented basterial infection
* Surgical care optimized with prothesis change or articular washing
* Infection requiring an antibiotic treatment by parenteral way Intravenous injection or per bone
* Treatment effective antibiotic begun in the most previously 21 days
* Signed consent

Exclusion Criteria:

* Patient with no proof of osteo-articular infection
* No surgical care
* Patient having more than one prothesis change because of sepsis
* Infection due to mycobactery, fungic infection or brucellienne infection
* Patient with life expectancy supposed lower than 2 years
* Guardianship patient
* Patient included in another study

Primary outcomes:
measure: occurrence of clinical cure
timeFrame: two years
Secondary outcomes:
measure: microbiological success
timeFrame: 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Service de chirurgie orthopédique et traumatologique, CHU d'AMIENS
city: Angers
country: France
facility: Service des maladies infectieuses et tropicales, CHU d'ANGERS
city: Antony
country: France
facility: Département de Médecine Interne et Maladies Infectieuses, hôpital privé d'Antony
city: Besançon
country: France
facility: Service des maladies infectieuses et tropicales, CHU de BESANCON
city: Beziers
country: France
facility: Service de médecine interne, CH de BEZIERS
city: Blois
country: France
facility: Service de chirurgie orthopédique et traumatologique, Polyclinique de BLOIS
city: Bordeaux
country: France
facility: Service de Maladies Infectieuses et de Médecine Tropicale, Hôpital Pellegrin, CHU de Bordeaux
city: Bourg-en-Bresse
country: France
facility: Service de chirurgie orthopédique et traumatologique, CH de BOURG EN BRESSE
city: Bourg-en-Bresse
country: France
facility: Service de Maladies Infectieuses, CH de BOURG EN BRESSE
city: Brest
country: France
facility: Service de médecine interne et de maladies infectieuses, CHU de BREST
city: Caen
country: France
facility: Service des maladies infectieuses et tropicales, CHU de CAEN
city: Chambery
country: France
facility: Service des maladies infectieuses et tropicales - médecine interne, CH de CHAMBERY
city: Châlon sur Saone
country: France
facility: Service de médecine interne, rhumatologie, Centre Hospitalier Chalon sur Saône William Morey
city: Clamart
country: France
facility: Service de Chirurgie Orthopédique et Traumatologique, APHP Hôpital Antoine Béclère
city: Clamart
country: France
facility: Service de Médecine Interne et Immunologie Clinique, APHP Hôpital Antoine Béclère
city: Clermont Ferrand
country: France
facility: Service des maladies infectieuses et tropicales, CH de CLERMONT-FERRAND
city: Illkirch GRAFFENSTADEN
country: France
facility: Centre de chirurgie orthopédique et de la main, CHRU de STRASBOURG
city: Lille
country: France
facility: Unité de Traumatologie -Orthopédie septique, CHRU de LILLE
city: Limoges
country: France
facility: Service de Maladies Infectieuses, CHU de LIMOGES
city: Lyon
country: France
facility: Centre de vaccinations internationales et de médecine des voyages du Tonkin
city: Montpellier
country: France
facility: Service des Maladies Infectieuses et tropicales, CHU de MONTPELLIER
city: Nancy
country: France
facility: Service des Maladies Infectieuses et tropicales, CHU de NANCY
city: Nantes
country: France
facility: Service des maladies infectieuses et tropicales Hôtel-Dieu, CHU de Nantes
city: Paris
country: France
facility: Service de Chirurgie orthopédique Hôpital Lariboisière
city: Perpignan
country: France
facility: Service des maladies infectieuses et tropicales CH Saint-Jean
city: Poitiers
country: France
facility: Service de médecine interne, maladies infections et tropicales, CHU de POITIERS
city: Pontoise
country: France
facility: Service de médecine interne, PONTOISE
city: Pringy
country: France
facility: Service des maldies infectieuses, CH d'ANNECY
city: Reims
country: France
facility: Service de Maladies Infectieuses, CHU de REIMS
city: Rennes
country: France
facility: Service des Maladies Infectieuses, CHU de RENNES
city: Saint Quentin
country: France
facility: Service de pneumologie - maladies infectieuses et tropicales, CH de ST QUENTIN
city: Toulon
country: France
facility: Service d'infectiologie, CH de TOULON
city: Toulouse
country: France
facility: Service de Chirurgie Orthopédique et Traumatologique
city: Tourcoing
country: France
facility: Service des maladies infectieuses CH Gustave Dron
city: Tours
country: France
facility: Service de Chirurgie Orthopédique et traumatologie, hôpital Trousseau
city: Tours
country: France
facility: Service de Médecine Interne et de Maladies Infectieuses, CHRU de TOURS
city: Versailles
country: France
facility: Service de chirurgie orthopédique, CH de VERSAILLES
Study officials:
References:
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.