Results of Extended Versus Single Dose Antibiotic Prophylaxis In Orthopedic Revision Arthroplasty in Nijmegen.

Phase 3

Active, not recruiting

• Conditions: Infection Prosthesis Hip and Knee; Infection, Prosthesis Related; Joint Infection; Infection, Surgical Site; Infection Pro; Surgical Site Infection
• Interventions: Drug: Cefazolin

• Registration Number: NCT06402591
• Lead Sponsor: Radboud University Medical Center

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)?

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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.

Study Timeline

• Study Start: 2019-01-01
• Study First Submitted: 2023-04-07
• Primary Completion: 2023-12-01
• Status Verified: 2024-05
• Study First Submitted QC: 2024-05-03
• Last Update Submitted: 2024-05-03
• Study First Posted: 2024-05-07
• Last Update Posted: 2024-05-07
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 751

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
extended cefazolin prophylaxis	Cefazolin	5 days of cefazolin prophylaxis start dose 2000mg followed by 14 doses of 1000mg

Primary Outcome Measures

Name	Time	Method
Success rate of revision arthroplasty	1 year after revision arthroplasty	1. Implant retention during follow-up,; 2. No 'definite infection' score for PJI according to the Philadelphia consensus definition 2018 during follow-up; 3. No PJI based on positive culture of a single synovial fluid or tissue sample yielding a high virulence micro-organism (S. aureus, Enterobacteriaceae, Pseudomonas spp, Acinetobacter spp, Candida spp) during follow-up.; 4. No more than 4 consecutive weeks of systemic antimicrobial therapy for any reason during follow-up.

Secondary Outcome Measures

Name	Time	Method
resistance rate of causative of SSI/PJI to cefazolin	1 year after revision arthroplasty	The cefazolin susceptibility of the micro-organisms causing SSI and PJI in the study groups.
incidence periprosthetic joint infection	1 year after revision arthroplasty	The proportion of PJI according to Philadelphia consensus definition 2018 in both study groups during follow-up.
The number of repeated surgeries.	1 year after revision arthroplasty	The number of repeated surgeries.
Reason repeated surgery	1 year after revision arthroplasty	The reason for repeated surgery on the affected prosthetic joint during follow-up.
adverse drug events	1 year after revision arthroplasty	Adverse drug events and serious adverse events.
Risk factors associated with SSI and PJI: BMI, age, age of implant before revision,	1 year after revision arthroplasty	Risk factors associated with SSI and PJI: BMI, age, age of implant before revision, number of previous revisions before index
Patient related outcome measurements	1 year after revision arthroplasty	PROMs at weeks 12 and 52
incidence surgical site infections	1 year after revision arthroplasty	a. The proportion of SSI according to PREZIES (PREventie van ZIEkenhuisinfecties door Surveillance) criteria in both study groups during follow-up.
Implant survival at the end of the study.	during inclusion of the study	Implant survival at the end of the study.

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Gelderland, Netherlands