Wound Infections Following Implant Removal

Study Overview
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Brief Summary
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In the Netherlands about 18,000 surgical procedures with implant removal are annually performed after fracture healing, of which 30-80% concern the foot, ankle and lower leg region. For clean surgical procedures, the rate of postoperative wound infections (POWIs) should be less than 5%. However, rates of 10-12% following implant removal, specifically after foot, ankle and lower leg fractures are reported. Currently, surgeons decide individually if antibiotics prophylaxis is given, since no guideline exists. This leads to undesirable practice variation. Therefore, the investigators propose a double-blind randomized controlled trial (RCT) in patients scheduled for implant removal following a foot, ankle or lower leg fracture, to assess the (cost-)effectiveness of a single gift of antibiotic prophylaxis. Primary outcome is a POWI within 30 days after implant removal. Secondary outcomes are quality of life, functional outcome at 30 days and 6 months after implant removal and costs. With 2 x 250 patients a decrease in POWI from 10% to 3.3% (expected rate in clean-contaminated elective orthopedic trauma procedures) can be detected (Power=80%, 2-sided alpha=5%, including 15% lost to follow up). If the assumption of the investigators, that prophylactic antibiotics prior to implant removal reduces the infectious complication rate, is confirmed by this RCT, this will offer a strong argument to adopt a single gift of antibiotic prophylaxis as standard practice of care. This will reduce the incidence of POWIs and consequently will lead to less physical and social disabilities and health care use. In addition, it will decrease the rate of use of empiric broad-spectrum antibiotics (and antibiotic resistance) prescribed upon suspicion or diagnosis of a POWI. A preliminary, conservative estimation suggests yearly cost savings in the Netherlands of €3.5 million per year.

Detailed Description
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See study protocol

Official Title
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Antibiotic Prophylaxis to Prevent Wound Infections Following Implant Removal

Conditions
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Surgical Wound Infection

Intervention / Treatment
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* Drug: Cephalozin
* Other: Sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥18 years and ≤75 years of all ethnic backgrounds Implant removal following foot, ankle and/or lower leg surgery Exclusion Criteria: Removing and re-implanting osteosynthesis material in the same session Active wound infection or (plate) fistula Antibiotic treatment at time of elective implant removal for a concomitant disease or infection A medical history of an allergic reaction to a cephalosporin, penicillin, or any other β-lactam antibiotic. Insufficient comprehension of the Dutch language to understand the patient information to make an informed decision to participate. Kidney disease (eGFR <60 ml/min/1.73m^2). Treatment with probenecide, anticoagulants (see SPC) Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: antibiotic prophylaxis<br>a single gift of 1000 mg cefazolin in 10 cc of NaCl 0.9% (intervention group) | Drug: Cephalozin<br>* 1000 mg Cephalozin<br>* Other names: Kefzol;|
| Placebo Comparator: No antibiotic prophylaxis<br>a single gift of 10 cc NaCl 0.9%, given in the same manner (control group). | Other: Sodium chloride<br>* 10 cc of NaCl 0.9%<br>* Other names: NaCl 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative wound infection (POWI) | The primary outcome variable is a POWI within 30 days after implant removal as defined by the criteria applied by the Centers for Disease and Control. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health-related quality of life | Health-related quality of life (as measured by the EQ-5D questionnaire) | baseline, one month, 6 months | 
| Functional outcome | Functional outcome following implant removal as assessed with the Lower Extremity Functional Scale (LEFS). The LEFS can be used by clinicians as a measure of patients' initial function, ongoing progress and outcome, as well as to set functional goals. The LEFS can be used to evaluate the functional impairment of a patient with a disorder of one or both lower extremities. It can be used to monitor the patient over time and to evaluate the effectiveness of an intervention | baseline, 1 month, 6 months | 
| Patient satisfaction | Patient satisfaction following implant removal as measured by a ten-point Visual Analog Scale | 1 month, 6 months | 
| Health care resources utilization | Health care resources utilization at baseline, 1 month and 6 months after implant removal (including amongst others, number of visits to the general practitioner and use of home care organizations) as measured by way of a combination of the Dutch iMTA Medical Consumption Questionnaire (iMCQ) and iMTA Productivity Cost Questionnaire (iPCQ) (adapted to the study setting). | baseline, 1 month, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implant Removal, Antibiotic Prophylaxis, Postoperative wound infection, Orthopedics