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

Multiple Doses Versus Single Dose of Cefazolin to Prevent Periprosthetic Joint Infection After Revision Arthroplasty: a Multicenter Open-label, Randomized Clinical Trial.

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].

Study Overview

• Status: Active, not recruiting
• Conditions: Surgical Site Infection; Joint Infection; Infection, Surgical Site; Infection Prosthesis Hip and Knee; Infection, Prosthesis Related; Infection Pro
• Intervention / Treatment: Drug: Cefazolin

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 Type: Interventional
• Enrollment (Actual): 751
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: single dose cefazolin prophylaxis; prophylaxis according current guidelines single dose 2000mg cefazolin 15-30 minutes before incision
Experimental: extended cefazolin prophylaxis; 5 days of cefazolin prophylaxis start dose 2000mg followed by 14 doses of 1000mg	Drug: Cefazolin; cefazolin extended prophylaxis 5 days (15 doses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success rate of revision arthroplasty	Implant retention during follow-up,; No 'definite infection' score for PJI according to the Philadelphia consensus definition 2018 during follow-up; 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.; No more than 4 consecutive weeks of systemic antimicrobial therapy for any reason during follow-up.	1 year after revision arthroplasty

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Sint Maartenskliniek
• Investigators: Principal Investigator: Bart-Jan Kullberg, prof. Dr, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): December 1, 2023
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 7, 2023
• First Submitted That Met QC Criteria: May 3, 2024
• First Posted (Actual): May 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 3, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Disease Attributes; Wound Infection; Infections; Communicable Diseases; Surgical Wound Infection; Prosthesis-Related Infections; Anti-Infective Agents; Anti-Bacterial Agents; Cefazolin
• Other Study ID Numbers: NL70114.091.19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No