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

Total Hip Arthroplasty Clinical Trial

— ProHipQ-F  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05530174
• Other study ID #: ProHipQ Fracture
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2022
• Est. completion date: July 1, 2025

Study information

• Verified date: December 2022
• Source: University Hospital Bispebjerg and Frederiksberg
• Contact: Armita A Abedi, MD
• Phone: +4551358644
• Email: armita.armina.abedi[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: July 1, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Fracture of Hip
• Fractures, Bone
• Hip Fractures
• Total Hip Arthroplasty

Intervention

Other:
• Antibiotic dosage practice
Patient inclusion starts day one, cross-over of departments from treatment A (single-dose) to B (multiple-dose) or vice versa after one year and end of inclusion happens after 2 years. All centers in Denmark use either Cloxacillin/Dicloxacillin, Cefuroxime or both drugs as standard prophylactic antibiotic practice for THA. In cases of cephalosporin allergy or general beta lactam allergy, the antibiotic clindamycin may be administered. In this trial, patients will be administered the standard prophylactic antibiotic practice of either single-dose (A) or multiple-doses (B) of antibiotics administered at each respective cluster that respective year. Both practices of dose administration for antibiotic prophylaxis (i.e. single- or multiple-dose) follow current standards of treatment and are based on present clinical practice guidelines.

Locations

Country	Name	City	State
Denmark	Department of Orthopedic Surgery, Aabenraa and Sønderborg, Hospital of Southern Jutland	Aabenraa
Denmark	Capio Private Hospital, Aalborg	Aalborg
Denmark	Department of Orthopedic Surgery, Aalborg, Aalborg University Hospital	Aalborg
Denmark	Aleris Private Hospital, Aarhus	Aarhus
Denmark	Deaprtment of Orthopaedic Surgery, Aarhus University Hospital	Aarhus
Denmark	Capio Private Hospital, Aarhus	Aarhus C
Denmark	Capio Private Hospital, Gildhøj	Brøndby
Denmark	Department of Orthopedic Surgery and Traumatology, Bispebjerg, Copenhagen University Hospital - Bispebjerg and Frederiksberg	Copenhagen NV
Denmark	Adeas Private Hospital, Parken	Copenhagen Ø
Denmark	Department of Orthopedic Surgery, Esbjerg, Hospital of South West Jutland	Esbjerg
Denmark	Department of Orthopedic Surgery, Farsø, Aalborg University Hospital	Farsø
Denmark	CPH Private Hospital	Farum
Denmark	Department of Orthopedic Surgery, Frederikshavn, Aalborg University Hospital	Frederikshavn
Denmark	Department of Orthopedic Surgery, Grindsted, Hospital of South West Jutland	Grindsted
Denmark	Capio Private Hospital, Hellerup and Odense	Hellerup
Denmark	Department of Orthopaedic Surgery, Gentofte, Copenhagen University Hospital - Herlev and Gentofte	Hellerup
Denmark	Department of Orthopaedic Surgery, Herlev, Copenhagen University Hospital - Herlev and Gentofte	Herlev
Denmark	Department of Orthopedic Surgery, Gødstrup Regional Hospital	Herning
Denmark	Department of Orthopedic Surgery, Hillerød, Copenhagen University Hospital - North Zealand	Hillerød
Denmark	Department of Orthopedic Surgery, Copenhagen University Hospital - Holbæk	Holbæk
Denmark	Department of Orthopedic Surgery, Horsens Regional Hospital, Denmark	Horsens
Denmark	Department of Orthopedic Surgery, Hvidovre, Copenhagen University Hospital - Amager and Hvidovre	Hvidovre
Denmark	Department of Orthopedic Surgery, Zealand University Hospital, Køge	Køge
Denmark	Acure Private Hospital	Kongens Lyngby
Denmark	Kollund Private Hospital, Kollund	Kruså
Denmark	Department for Planned Orthopaedic Surgery, Næstved, Copenhagen University Hospital - Næstved, Slagelse and Ringsted	Næstved
Denmark	Department of Orthopedic Surgery, Copenahegn University Hospital - Nykøbing F.	Nykøbing Falster
Denmark	Department of Orthopedic Surgery and Traumatology, Odense University Hospital and Svendborg Hospital	Odense
Denmark	Deparmtent of Orthopedic Surgery, Randers Regional Hospital	Randers
Denmark	Aleris Private Hospital, Ringsted	Ringsted
Denmark	Department of Surgery, Copenhagen University Hospital - Bornholm	Rønne
Denmark	Center for Planned Surgery, Silkeborg Regional Hospital	Silkeborg
Denmark	Aleris Private Hospital, Søborg	Søborg
Denmark	Department of Orthopedics, Lillebaelt Hospital, Vejle	Vejle
Denmark	Mølholm Private Hospital, Vejle	Vejle
Denmark	Deparmtent of Orthopedic Sugery, Viborg Regional Hospital	Viborg

Sponsors (7)

Lead Sponsor	Collaborator
Soren Overgaard	Aarhus University Hospital, Odense University Hospital, Sygehus Lillebaelt, University Hospital Bispebjerg and Frederiksberg, University of Aarhus, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incremental cost-effectiveness	The incremental cost-effectiveness will be calculated based on the costs per patient in the two antibiotic practices. Costs related to antibiotic prophylaxis, hospital admissions and readmissions, hospital outpatient visits, visits to General practitioner and costs related to sick leave from work will be included.; Data will be collected from: The Danish National Patient Registry (DNPR); The Civil Registration System (CRS); The Danish Agency for Labor Market and Recruitment registry STAR	Within 90 days from index surgery
Other	Rate of revision after THA	Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of the implant. Revision due to any cause including PJI and aseptic loosening are included.; Revision risk is recorded from DHR and DNPR.	Within 1 year from index surgery
Other	Mortality rate after index surgery	1-year mortality rate is defined by date of death due to any cause after index surgery. Data is collected from The Civil Registration System (CRS).	Within 1 year from index surgery
Other	Incidence of Superficial incisional Surgical Site Infection	To be defined	Within 90 days from index surgery
Primary	Incidence of Prosthetic joint infections (PJI)	The definition of PJI is based on revision surgery. Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of the implant.; The definition of PJI is based on revision surgery. Revision surgery is defined as a new surgical intervention the first time after the primary intervention including debridement alone or in combination with complete or partial removal or exchange of the implant.; Two or more intraoperative deep-tissue samples of phenotypically indistinguishable bacteria isolated from at least 3 deep-tissue samples; One or more positive intraoperative samples from a closed fluid aspirate AND a biopsy (fluid AND tissue) of phenotypically indistinguishable bacteria isolated; A PJI when an indication of deep infection is reported to The Danish Hip Arthroplasty Registry (DHR) by the surgeon upon revision surgery	Within 90 days from index surgery
Secondary	Number of patients with one or more Serious Adverse Events (SAEs)	SAEs are defined according to the ICH-GCP guidelines. SAE refers to an event involving a significant risk of death or disability of the patient (or their offspring), including, but not limited to, an event that: results in death; is life-threatening - in the investigator's opinion the patient was in immediate risk of death from the adverse event when it appeared; requires hospitalization or prolongs existing hospitalization; results in permanent or significant disability; is a congenital anomaly SAEs are recorded from The Danish National Patient Registry (DNPR).	Within 90 days from index surgery
Secondary	Incidence of Potential PJI referred to as PJI-likely	PJI-likely is defined as at least one of the two criteria: One single intraoperatively obtained positive culture (aspiration fluid OR tissue biopsy) regardless of microorganism; One single positive culture obtained from aspiration of synovial fluid regardless of microorganism AND any antibiotic prescriptions (ATC category J01) redeemed	Within 90 days from index surgery
Secondary	Length of hospital stay (LOS)	LOS defined as number of postoperative overnight stays, including transferals to other departments and hospitals. Data on LOS is acquired from DNPR.	Within 90 days from index surgery
Secondary	Incidence of Thromboembolic complications incl VTE, MI, AF, stroke	VTE is defined a priori as both deep venous thromboembolisms confirmed by compression ultrasound and pulmonary embolism confirmed by spiral computed tomography (CT), ventilation-perfusion scintigraphy or pathological removal of an embolus and based on the following diagnostic ICD10 codes: I26, I80.1-I80.9, I82.1-I82.9, or T81.7B-D. Data will be extracted from DNPR.	Within 90 days from index surgery
Secondary	Hospital-treated infections (excluding Surgical Site infections)	Any Hospital-treated infection is defined as any first-time hospital admission with a primary or secondary infection diagnosis after discharge from index THA surgery. Hospital-treated infections are identified from DNPR.; The list of infections includes chronic and more rare infections, to detect possible flare-up in any possible ongoing infections.; The list will exclude urinary tract infections (UTI) due to a high risk of different registration praxis registration for UTI among hospitals in Denmark.	Within 90 days from index surgery
Secondary	Proportion of patients with at least one dispensing for antibiotic	Community-based antibiotic use (any community-treated infection or antibiotic use after discharge) is defined as at least one dispensing after discharge from index THA surgery within 90 days for narrow- and broad-spectrum antibiotics based on the Anatomical Therapeutic Chemical classification (ATC) codes. All antibiotics in Denmark require prescriptions from a physician. The Danish National Health Service Prescription Database has registered all reimbursed prescriptions from all community pharmacies since 2004. Medications are coded according to the following ATC codes: J01CE, J01CF, J01DB, J01DC, J01DD, J01DE, J01DH, J01DI, J01CR, J01CA, J01F. J01E, J01MA ,J01AA	Within 90 days from index surgery
Secondary	Proportion of patients with a least one dispensing for opioids	Prescriptions redeemed is defined as at least 1 prescription dispensing of any opioid. Prescriptions of analgesics will be identified through The Danish National Prescription Registry. The registry contains information on all prescriptions redeemed by Danish residents in community pharmacies since 1995 (excluding hospital dispensaries). Information on Anatomical Classification System (ATC) codes and dispensation date will be applied to identify opioids. Following ATC codes (including all sub codes) are included: N01AH (opioid anesthetics), N02A (opioids), N07BC02 (methadone), and R05DA04 (codeine). Duration of treatment will be calculated based on no. of packages and volume.	Within 90 days from index surgery
Secondary	Proportion of patients with dispensing for acetaminophen or non-steroid anti-inflammatory drug	Prescription redeemed is defined as at least 1 prescription dispensing of any acetaminophen or NSAID within 90 days after index THA surgery. Prescriptions of analgesics are identified using the Danish National Prescription Registry. Information on Anatomical Classification System (ATC) codes and dispensation date will be applied to identify acetaminophen and NSAID. Following ATC codes (including all sub codes) are included M01A (NSAIDs). Duration of treatment will be calculated based on no. of packages and volume.	Within 90 days from index surgery