Effect of Single vs Multiple Prophylactic Antibiotic Doses on PJI Following Primary THA in Patients With OA (ProHipQ-OA)

December 2, 2022 updated by: Soren Overgaard

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

Aim: To compare the effect of one single dose versus multiple doses of prophylactic antibiotics administered within 24 hours, on the development of PJI in patients with osteoarthritis undergoing primary THA.

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 20,000 primary THAs conducted at all public and private orthopedic departments in Denmark, this includes 36 sites corresponding to a total of 39 departments.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 may be 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.

After the first postoperative dose, the remaining doses may be administered perorally for pragmatic reasons. Administration of peroral doses as followed regardless of weight:

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 may be 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.

Study Type

Interventional

Enrollment (Anticipated)

20000

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Denmark
      • Aabenraa, Denmark, 6200/6400
        • Recruiting
        • Department of Orthopedic Surgery, Hospital of Southern Jutland, Aabenraa and Sønderborg
        • Contact:
        • Contact:
      • Aalborg, Denmark, 9000
        • Recruiting
        • Capio Private Hospital, Aalborg
        • Contact:
        • Contact:
          • Poul T Nielsen, MD
          • Phone Number: +4598392244
          • Email: ptn@capio.dk
      • Aalborg, Denmark, 9000
        • Recruiting
        • Department of Orthopedic Surgery, Aalborg, Aalborg University Hospital
        • Contact:
        • Contact:
      • Aarhus, Denmark, 8200
      • Aarhus, Denmark, 8200
        • Recruiting
        • Deaprtment of Orthopaedic Surgery, Aarhus University Hospital
        • Contact:
        • Contact:
          • Stig S Jakobsen, MD, PhD
          • Phone Number: +4540976165
          • Email: stigjako@rm.dk
      • Aarhus C, Denmark, 8000
      • Brøndby, Denmark, 2605
        • Recruiting
        • Capio Private Hospital, Gildhøj
        • Contact:
        • Contact:
          • Micael Haugegaard, MD
          • Phone Number: +4570878328
          • Email: mh@gildhoj.dk
      • Copenhagen NV, Denmark, 2400
        • Recruiting
        • Department of Orthopedic Surgery and Traumatology, Bispebjerg, Copenhagen University Hospital - Bispebjerg and Frederiksberg
        • Contact:
        • Contact:
      • Copenhagen Ø, Denmark, 2100
        • Recruiting
        • Adeas Private Hospital, Parken
        • Contact:
        • Contact:
          • Anne Marie Sørensen, MD, PhD
          • Phone Number: +4588774000
          • Email: ams@adeas.dk
      • Esbjerg, Denmark, 6700
      • Farsø, Denmark, 9640
        • Recruiting
        • Department of Orthopedic Surgery, Farsø, Aalborg University Hospital
        • Contact:
        • Contact:
      • Farum, Denmark, 3520
      • Frederikshavn, Denmark, 9900
        • Recruiting
        • Department of Orthopedic Surgery, Frederikshavn, Aalborg University Hospital
        • Contact:
        • Contact:
      • Grindsted, Denmark, 7200
      • Hellerup, Denmark, 2900/5000
        • Recruiting
        • Capio Private Hospital, Hellerup and Odense
        • Contact:
        • Contact:
          • Christian Hofbauer, MD
          • Phone Number: +4539777070
          • Email: cho@capio.dk
      • Hellerup, Denmark, 2900
      • Herlev, Denmark, 2730
      • Herning, Denmark, 7400
      • Hillerød, Denmark, 3400
      • Holbæk, Denmark, 4300
        • Recruiting
        • Department of Orthopedic Surgery, Copenhagen University Hospital - Holbæk
        • Contact:
        • Contact:
      • Horsens, Denmark, 8700
        • Recruiting
        • Department of Orthopedic Surgery, Horsens Regional Hospital, Denmark
        • Contact:
        • Contact:
          • Jeppe Lange, MD, PhD
          • Phone Number: +4526853290
          • Email: jepplang@rm.dk
      • Hvidovre, Denmark, 2650
      • Kongens Lyngby, Denmark, 2800
      • Kruså, Denmark, 6340
      • Køge, Denmark, 4600
      • Nykøbing Falster, Denmark, 4800
        • Recruiting
        • Department of Orthopedic Surgery, Copenahegn University Hospital - Nykøbing F
        • Contact:
        • Contact:
      • Næstved, Denmark, 4700
        • Recruiting
        • Department for Planned Orthopaedic Surgery, Næstved, Copenhagen University Hospital - Næstved, Slagelse and Ringsted
        • Contact:
        • Contact:
      • Odense, Denmark, 5000/5700
      • Randers, Denmark, 8930
        • Recruiting
        • Deparmtent of Orthopedic Surgery, Randers Regional Hospital
        • Contact:
        • Contact:
      • Ringsted, Denmark, 4100
      • Rønne, Denmark, 3700
      • Silkeborg, Denmark, 8600
        • Recruiting
        • Center for Planned Surgery, Silkeborg Regional Hospital
        • Contact:
        • Contact:
          • Peter B Hollænder, MD
          • Phone Number: +4521558580
          • Email: peterlar@rm.dk
      • Søborg, Denmark, 2860
      • Vejle, Denmark, 7100
      • Vejle, Denmark, 7100
      • Viborg, Denmark, 8800

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1. All patients receiving a primary Total Hip Arthroplasty (THA) due to primary and secondary causes of osteoarthritis

Exclusion Criteria:

  1. Patients receiving a primary THA due to either acute or sequelae of proximal femoral or acetabular fractures
  2. Patients receiving a primary THA due to bone tumor or metastasis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment A, Single-dose practice

One preoperative single dose of either Dicloxacillin/Cloxacillin 2g OR Cefuroxime 1.5g administered intravenously prior to surgical incision.

As the study is a non-inferiority trial, we have chosen the Experimental design category.
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.
Active Comparator: Treatment B, Multiple-dose practice
One preoperative dose of either Dicloxacillin/Cloxacillin 2g OR Cefuroxime 1.5g administered intravenously prior to surgical incision followed by 3 postoperative doses of Dicloxacillin/Cloxacillin 1g x 3 OR Cefuroxime 750mg x 3 within 24 hours after the preoperative dose.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Prosthetic joint infections (PJI)
Time Frame: Within 90 days from index surgery

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.

  1. Two or more intraoperative deep-tissue samples of phenotypically indistinguishable bacteria isolated from at least 3 deep-tissue samples
  2. One or more positive intraoperative samples from a closed fluid aspirate AND a biopsy (fluid AND tissue) of phenotypically indistinguishable bacteria isolated
  3. 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with one or more Serious Adverse Events (SAEs)
Time Frame: Within 90 days from index surgery

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
Incidence of Potential PJI referred to as PJI-likely
Time Frame: Within 90 days from index surgery

PJI-likely is defined as at least one of the two criteria:

  1. One single intraoperatively obtained positive culture (aspiration fluid OR tissue biopsy) regardless of microorganism
  2. 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
Length of hospital stay (LOS)
Time Frame: Within 90 days from index surgery
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
Incidence of Thromboembolic complications incl VTE, MI, AF, stroke
Time Frame: Within 90 days from index surgery
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
Hospital-treated infections (excluding Surgical Site infections)
Time Frame: Within 90 days from index surgery

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
Proportion of patients with at least one dispensing for antibiotic
Time Frame: Within 90 days from index surgery
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
Proportion of patients with a least one dispensing for opioids
Time Frame: Within 90 days from index surgery
Prescription 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
Proportion of patients with dispensing for acetaminophen or non-steroid anti-inflammatory drug
Time Frame: Within 90 days from index surgery
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incremental cost-effectiveness
Time Frame: Within 90 days from index surgery

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
Rate of revision after THA
Time Frame: Within 1 year from index 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 rate of revision is recorded from The Danish Hip Arthroplasty Registry (DHR) and The Danish National Patient Registry (DNRP). Revision due to any cause including PJI and aseptic loosening will be included.
Within 1 year from index surgery
Mortality rate after index surgery
Time Frame: Within 1 year from 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
Incidence of Superficial incisional Surgical Site Infection
Time Frame: Within 90 days from index surgery
To be defined
Within 90 days from index surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Soren Overgaard

Collaborators

Odense University Hospital
Aarhus University Hospital
University of Copenhagen
University of Aarhus
University Hospital Bispebjerg and Frederiksberg
Sygehus Lillebaelt

Investigators

  • Principal Investigator: Armita A Abedi, MD, Copenhagen University Hospital Bispebjerg, Department of Orthopaedic Surgery and Traumatology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2022

Primary Completion (Anticipated)

November 30, 2024

Study Completion (Anticipated)

July 1, 2025

Study Registration Dates

First Submitted

August 30, 2022

First Submitted That Met QC Criteria

September 3, 2022

First Posted (Actual)

September 7, 2022

Study Record Updates

Last Update Posted (Actual)

December 5, 2022

Last Update Submitted That Met QC Criteria

December 2, 2022

Last Verified

December 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ProHipQ Osteoarthritis

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), will be provided to anyone who wishes to access the data.

IPD Sharing Time Frame

Immediately following publication, no end date.

IPD Sharing Access Criteria

Anyone who wishes to access the data.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Osteoarthritis, Hip

Clinical Trials on Antibiotic dosage practice

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Qatar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe