Clinical trial NCT06402591: Results of Extended Versus Single Dose Antibiotic Prophylaxis In Orthopedic Revision Arthroplasty in Nijmegen.
Official title: Multiple Doses Versus Single Dose of Cefazolin to Prevent Periprosthetic Joint Infection After Revision Arthroplasty: a Multicenter Open-label, Randomized Clinical Trial.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Infection Prosthesis Hip and Knee
Infection, Prosthesis Related
Joint Infection
Infection, Surgical Site
Surgical Site Infection
Infection Pro
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Sint Maartenskliniek
First posted: 2024-05-07
Enrollment: 751
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: randomized controled trial
Primary purpose: PREVENTION

Brief summary: The goal of this randomized control trial is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin prophylaxis in revision arthroplasty of the hip and knee. The main question\[s\] it aims to answer are:

* Is an extended regimen compared to a single dose of cefazolin associated with an increased infection-free implant survival within one year after index revision arthroplasty of the hip or knee?
* What are the incidence, risk factors, treatment outcome and prognosis of surgical site infections and periprosthetic joint infection during follow-up?
* What is the safety and tolerance of the antimicrobial prophylaxis regimens used?
* What are the antimicrobial susceptibility patterns of micro-organisms causing PJI during follow-up?
* What is the patient' physical performance and satisfaction of subjects within 1 year after the index revision arthroplasty, using patient related outcome measurements (PROMS)?

\[question 2\] Participants will \[describe the main tasks participants will be asked to do, treatments they'll be given and use bullets if it is more than 2 items\]. If there is a comparison group: Researchers will compare \[insert groups\] to see if \[insert effects\].

Detailed description: Periprosthetic joint infection (PJI) is an important complication of total joint arthroplasty of the hip and knee and occurs in 1-2% after primary arthroplasty and in 10-15% after revision arthroplasty. To prevent a PJI, peri-operative antibiotic prophylaxis is given. There's inadequate evidence for a recommendation about the optimal duration of prophylaxis, especially in revision arthroplasty. The aim of this multicenter open-label, randomized controlled trial is to investigate the superiority of 5 days (extended) versus a single dose of cefazolin prophylaxis in revision arthroplasty of the hip and knee. Patients will be recruited at the orthopedic departments of two Dutch hospitals, University Medical Center Radboudumc Nijmegen (Radboudumc) and Sint Maartenskliniek in Nijmegen (SMK). Patients will be included if they will undergo revision arthroplasty of the hip or knee, with exclusion of patients with a proven PJI at baseline. A total of 780 subjects will be randomized between 2 prophylactic strategies: A) Cefazolin at a single dose of 2 grams intravenously 15-60 minutes before incision; B) Cefazolin at a dose of 2 grams intravenously 15-60 minutes before incision, followed by cefazolin 1 gram intravenously t.i.d. until five days post-surgery. The primary endpoint is the difference in proportion of infectious-free implant survival between both groups within 1 year of follow-up.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 years or older.
2. Planned revision arthroplasty of the hip or knee prosthesis (index revision arthroplasty), with revision of one or more fixed components.

Exclusion Criteria:

1. If the index revision arthroplasty has been cancelled.
2. Revision of single mobile parts only.
3. PJI on baseline, based on 'definite infection' score according to the Philadelphia consensus definition 2018
4. PJI on baseline, based on a positive culture of a single synovial fluid or tissue sample yielding a high virulence micro-organism (S. aureus, Enterobacterales, Pseudomonas spp, Acinetobacter spp, Candida spp).
5. Contraindication to cefazolin:

a. Previous allergic reaction according to the criteria in Appendix A. b. Severe kidney disease defined as eGFR \<10 ml/min. f. Antimicrobial treatment within 3 days prior to index revision arthroplasty. g. Subjects who are currently enrolled in investigational immunosuppressive drug trials.

h. Subjects who are unable to provide informed consent.

Primary outcomes:
measure: Success rate of revision arthroplasty
timeFrame: 1 year after revision arthroplasty
Secondary outcomes:
measure: incidence surgical site infections
timeFrame: 1 year after revision arthroplasty
measure: incidence periprosthetic joint infection
timeFrame: 1 year after revision arthroplasty
measure: resistance rate of causative of SSI/PJI to cefazolin
timeFrame: 1 year after revision arthroplasty
measure: The number of repeated surgeries.
timeFrame: 1 year after revision arthroplasty
measure: Reason repeated surgery
timeFrame: 1 year after revision arthroplasty
measure: adverse drug events
timeFrame: 1 year after revision arthroplasty
measure: Risk factors associated with SSI and PJI: BMI, age, age of implant before revision,
timeFrame: 1 year after revision arthroplasty
measure: Implant survival at the end of the study.
timeFrame: during inclusion of the study
measure: Patient related outcome measurements
timeFrame: 1 year after revision arthroplasty
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Bart-Jan Kullberg, prof. Dr
role: PRINCIPAL_INVESTIGATOR
References: