RESEARCH QUESTION: What is the (cost-)effectiveness of a single intravenous dose of 2g of cefazolin on SSIs prior to implant removal (IR) following osteosynthesis below the level of the knee?
HYPOTHESIS: 2g of prophylactic cefazolin is superior to placebo in the prevention of SSIs in IR below the level of the knee.
STUDY DESIGN: Multicenter, double blind, randomized controlled trial.
STUDY POPULATION: Adult patients scheduled for IR following osteosynthesis of foot, ankle, lower leg or patella.
INTERVENTION: A single dose of 2g of intravenously administered cefazolin as surgical prophylaxis, compared to a placebo.
OUTCOME MEASURES: Primary outcome is the number of SSI (deep/superficial) within 90 days. Secondary outcomes include wound healing problems, target-site concentration of antibiotics, presence of pathogens on the implant, quality of life, patient satisfaction and healthcare resource utilization and costs.
SAMPLE SIZE/DATA-ANALYSIS: To demonstrate a 50% reduction in both superficial and deep infections with a power of 80% and an alpha of 5%, accounting for 5% loss to follow up, the required number of patients is 732. The primary outcome will be corrected for center and analyzed using a logistic regression. A subgroup analysis will be performed for weight.
ECONOMIC EVALUATION: A cost-effectiveness (CEA) and a cost-utility (CUA) analysis will be performed from both a healthcare and a societal perspective. Medical costs, patient costs and productivity losses will be included in the evaluation. The affordability of antibiotic prophylaxis for IR will be assessed from governmental and insurer perspectives following a budget impact analysis.