Effect of Single vs Multiple Prophylactic Antibiotic Doses on PJI Following Primary THA in Patients With a Fracture

The Effect of Single vs Multiple Prophylactic Antibiotic Doses on PJI Following Primary THA in Patients With a Fracture: A Cross-over, Cluster Randomized Controlled, Non-inferiority Trial Based on National Quality Databases: ProHipQ-F

Aim: To compare the effect of one single dose versus multiple doses of prophylactic antibiotics administered within 24 hours, on the development of PJI after surgery in patients undergoing primary THA due to an acute fracture or sequelae of proximal femoral or acetabular fractures.

The study is designed as a cross-over, cluster randomized, non-inferiority trial. All Danish orthopedic surgery departments performing primary THA with the majority being within inclusion criteria will be involved: Based on national quality databases, two-year cohorts of approximately 2,000 primary THAs due to a fracture or sequelae to a fracture, conducted at all public and private orthopedic departments in Denmark, this includes 36 sites corresponding to a total of 39 departments.

The outcome measures will be extracted from the following national databases: The Civil Registration System (CRS), The Danish Hip Arthroplasty Register (DHR), The Danish National Patient Registry (DNRP), The Hospital Acquired Infections Database (HAIBA), The Danish National Prescription Database (NPR), Statistics Denmark and Danish Agency for Labour Market and Recruitment registry (STAR).

Details regarding the Arms and Interventions:

The preoperative dose of antibiotic must be administered prior to surgical incision and in cases of delay with regards to planned surgical incision:

Dicloxacillin/Cloxacillin: If the preoperative antibiotic dose is administered >60 minutes prior to surgical incision, the initial dose must be repeated.

Cefuroxime: If the preoperative antibiotic dose is administered >90 minutes prior to surgical incision, the initial dose must be repeated.

Treatment A, Single-dose practice:

For patients ≥ 120 kg:

One preoperative single dose of either Dicloxacillin/Cloxacillin 3g OR Cefuroxime 3g administered intravenously prior to surgical incision.

In cases of cephalosporin allergy or general beta lactam allergy one preoperative single dose of Clindamycin 900mg administered intravenously, prior to surgical incision, regardless of weight.

Treatment B, Multiple-dose practice:

For patients ≥ 120 kg:

One preoperative single dose of either Dicloxacillin/Cloxacillin 3g OR Cefuroxime 3g administered intravenously prior to surgical incision, followed by 3 postoperative doses of Dicloxacillin/Cloxacillin 2g x 3 OR cefuroxime 1.5g x 3, administered within 24 hours after the preoperative dose, corresponding to 6, 12 and 18 hours postoperatively.

After the first postoperative dose, the remaining doses may be administered perorally for pragmatic reasons.

Dicloxacillin p.o. 1g, 12 and 18 hours postoperatively. OR Amoxicillin and clavulanic acid p.o. 875mg/125*mg, 12 and 18 hours postoperatively.

*If the center or region does not have access to amoxicillin and clavulanic acid 875/125mg a dose of 1g / 125mg (this means amoxicillin 500mg + amoxicillin and clavulanic acid 500mg/125 mg) may be administered.

In cases of cephalosporin allergy or general beta lactam allergy one preoperative single dose of Clindamycin 900mg administered intravenously, prior to surgical incision, regardless of weight, followed by 2 postoperative doses corresponding to:

For patients <120kg: 300mg, 8 and 16 hours postoperatively. For patients ≥ 120kg: 600mg, 8 and 16 hours postoperatively. The same doses apply in cases of transmission to peroral antibiotics.

Implementation: The senior biostatistician is responsible for the randomization process of the centers. Each center will be allocated a code by the senior biostatistician responsible and reported to a central database. The randomization and allocation procedure will be known for the given year conditioning the given center.

Ethics and Dissemination: This trial has been approved by the Regional Ethical Committee (VEK) (21069108) and The Danish Medicines Agency (2021091723) without imposing an obligation to notify.

Inclusion Criteria:

• All patients receiving a primary Total Hip Arthroplasty (THA) due to an acute- or sequelae of proximal femoral or acetabular fractures

Exclusion Criteria:

• Patients receiving a primary THA due to bone tumor or metastasis
• Patients receiving a primary THA due to osteoarthritis and all reasons according to the Danish Hip Arthroplasty Register (DHR) except conditions mentioned in the inclusion criteria