Multiple doses versus single dose of cefazolin to prevent periprosthetic joint infection after revision arthroplasty: a multicenter open-label, randomized clinical trial

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 single dose prophylaxis follows the recommendation
of the recent international guidelines and is therefore registered as control.

We hypothesize that the extended antibiotic prophylactic regimen is associated
with increased infection-free survival of the implant within one year after
revision arthroplasty (index revision arthroplasty) compared to a single dose.

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.

This study is a multicenter open-label, randomized controlled superiority
trial. Subjects will be randomized in a 1:1 ratio to the extended prophylaxis
group and the single dose group (control). Randomization will be based on block
randomization stratified by hospital of intervention (Radboudumc or SMK) and
anatomic location of index revision arthroplasty (knee or hip). Subjects will
be recruited at the orthopedic surgery departments of Radboudumc and SMK.

In this study subjects, orthopedic surgeons and investigators are not blinded.
However, the evaluation of data for the primary outcome will be done by an
Independent Data Review Committee (DRC), blinded for randomization.

After obtaining informed consent, subjects will be randomized into 2
prophylactic groups:

A. Cefazolin at a single dose of 2 grams intravenously 15-60 minutes before
incision, with a repeat dose of 2 grams if the duration of the procedure is
more than 4 hours or when blood loss during the procedure is more than 1500ml.

B. Cefazolin at a dose of 2 grams intravenously 15-60 minutes before incision,
with a repeat dose of 2 grams if the duration of the procedure is more than 4
hours or when blood loss during the procedure is more than 1500ml. This will be
followed by cefazolin 1 gram intravenously t.i.d. until five days post-surgery.
In case of impaired kidney function and obesity, dose adjustment will be
performed.

- The proportion of SSI and PJI in both study groups during follow-up.
- The cefazolin susceptibility of the micro-organisms causing SSI and PJI in
the study groups.
- The number of repeated surgeries.
- The reason for repeated surgery on the affected prosthetic joint during
follow-up.
- Adverse drug events and serious adverse events.
- Risk factors associated with SSI and PJI.
- PROMs at weeks 12 and 52.