Clinical trial NCT05530174: Effect of Single vs Multiple Prophylactic Antibiotic Doses on PJI Following Primary THA in Patients With a Fracture
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Fracture of Hip
Total Hip Arthroplasty
Prosthetic-joint Infection
Fracture Acetabular
Keywords: Antibiotic Prophylaxis
Hip Fracture
Acetabular Fracture
Total Hip Replacement
Total Hip Arthroplasty
Prosthetic Joint Infection
PJI
Cluster Randomized Controlled Trial
Randomized Controlled Trial
RCT
THA
Lead sponsor: University Hospital Bispebjerg and Frederiksberg
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: University Hospital Bispebjerg and Frederiksberg
name: Odense University Hospital
name: Aarhus University Hospital
name: University of Aarhus
name: Sygehus Lillebaelt
First posted: 2022-09-07
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The Pro-Hip-Quality Trial is a Cluster Randomized Trial with an embedded Cross-Over Design where each clinical center (C: 1, 2, 3, ...., 36 individual sites) will be running a specific intervention (i.e. single- or multiple-dose antibiotics) throughout 12 months, and the subsequent year the clinical department will automatically switch to the opposite intervention (i.e. multiple- or single-dose antibiotics).
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Prosthetic joint infections (PJI)
timeFrame: Within 90 days from index surgery
Secondary outcomes:
measure: Number of patients with one or more Serious Adverse Events (SAEs)
timeFrame: Within 90 days from index surgery
measure: Incidence of Potential PJI referred to as PJI-likely
timeFrame: Within 90 days from index surgery
measure: Length of hospital stay (LOS)
timeFrame: Within 90 days from index surgery
measure: Incidence of Major Adverse Cardiovascular Events (MACE)
timeFrame: Within 90 days from index surgery
measure: Hospital-treated infections (excluding Surgical Site infections)
timeFrame: Within 90 days from index surgery
measure: Proportion of patients with at least one dispensing for antibiotic
timeFrame: Within 90 days from index surgery
measure: Opioid use
timeFrame: Within 90 days from index surgery
measure: Use of acetaminophen or non-steroidal anti-inflammatory drugs
timeFrame: Within 90 days from index surgery
measure: Any revision after THA
timeFrame: Within 90 days from index surgery
Other outcomes:
measure: Incremental cost-effectiveness
timeFrame: Within 90 days from index surgery
measure: Rate of revision after THA
timeFrame: Within 1 year from index surgery
measure: Mortality rate after index surgery
timeFrame: Within 1 year from index surgery
measure: Incidence of Superficial incisional Surgical Site Infection
timeFrame: Within 90 days from index surgery
Locations:
city: Aabenraa
country: Denmark
facility: Department of Orthopedic Surgery, Aabenraa and Sønderborg, Hospital of Southern Jutland
city: Aalborg
country: Denmark
facility: Capio Private Hospital, Aalborg
city: Aalborg
country: Denmark
facility: Department of Orthopedic Surgery, Aalborg, Aalborg University Hospital
city: Aarhus C
country: Denmark
facility: Capio Private Hospital, Aarhus
city: Aarhus
country: Denmark
facility: Aleris Private Hospital, Aarhus
city: Aarhus
country: Denmark
facility: Deaprtment of Orthopaedic Surgery, Aarhus University Hospital
city: Brøndby
country: Denmark
facility: Capio Private Hospital, Gildhøj
city: Copenhagen NV
country: Denmark
facility: Department of Orthopedic Surgery and Traumatology, Bispebjerg, Copenhagen University Hospital - Bispebjerg and Frederiksberg
city: Copenhagen Ø
country: Denmark
facility: Adeas Private Hospital, Parken
city: Esbjerg
country: Denmark
facility: Department of Orthopedic Surgery, Esbjerg, Hospital of South West Jutland
city: Farsø
country: Denmark
facility: Department of Orthopedic Surgery, Farsø, Aalborg University Hospital
city: Farum
country: Denmark
facility: CPH Private Hospital
city: Frederikshavn
country: Denmark
facility: Department of Orthopedic Surgery, Frederikshavn, Aalborg University Hospital
city: Grindsted
country: Denmark
facility: Department of Orthopedic Surgery, Grindsted, Hospital of South West Jutland
city: Hellerup
country: Denmark
facility: Capio Private Hospital, Hellerup and Odense
city: Hellerup
country: Denmark
facility: Department of Orthopaedic Surgery, Gentofte, Copenhagen University Hospital - Herlev and Gentofte
city: Herlev
country: Denmark
facility: Department of Orthopaedic Surgery, Herlev, Copenhagen University Hospital - Herlev and Gentofte
city: Herning
country: Denmark
facility: Department of Orthopedic Surgery, Gødstrup Regional Hospital
city: Hillerød
country: Denmark
facility: Department of Orthopedic Surgery, Hillerød, Copenhagen University Hospital - North Zealand
city: Holbæk
country: Denmark
facility: Department of Orthopedic Surgery, Copenhagen University Hospital - Holbæk
city: Horsens
country: Denmark
facility: Department of Orthopedic Surgery, Horsens Regional Hospital, Denmark
city: Hvidovre
country: Denmark
facility: Department of Orthopedic Surgery, Hvidovre, Copenhagen University Hospital - Amager and Hvidovre
city: Kongens Lyngby
country: Denmark
facility: Acure Private Hospital
city: Kruså
country: Denmark
facility: Kollund Private Hospital, Kollund
city: Køge
country: Denmark
facility: Department of Orthopedic Surgery, Zealand University Hospital, Køge
city: Nykøbing Falster
country: Denmark
facility: Department of Orthopedic Surgery, Copenahegn University Hospital - Nykøbing F.
city: Næstved
country: Denmark
facility: Department for Planned Orthopaedic Surgery, Næstved, Copenhagen University Hospital - Næstved, Slagelse and Ringsted
city: Odense
country: Denmark
facility: Department of Orthopedic Surgery and Traumatology, Odense University Hospital and Svendborg Hospital
city: Randers
country: Denmark
facility: Deparmtent of Orthopedic Surgery, Randers Regional Hospital
city: Ringsted
country: Denmark
facility: Aleris Private Hospital, Ringsted
city: Rønne
country: Denmark
facility: Department of Surgery, Copenhagen University Hospital - Bornholm
city: Silkeborg
country: Denmark
facility: Center for Planned Surgery, Silkeborg Regional Hospital
city: Søborg
country: Denmark
facility: Aleris Private Hospital, Søborg
city: Vejle
country: Denmark
facility: Department of Orthopedics, Lillebaelt Hospital, Vejle
city: Vejle
country: Denmark
facility: Mølholm Private Hospital, Vejle
city: Viborg
country: Denmark
facility: Deparmtent of Orthopedic Sugery, Viborg Regional Hospital
Study officials:
affiliation: Copenhagen University Hospital, Bispebjerg Department of Orthopedic Surgery and Traumatology
name: Armita A Abedi, MD
role: PRINCIPAL_INVESTIGATOR
References: