The Effectiveness of Antibiotic Cement (ABC) Compared to Regular Cement in Reducing the Rate of Infection Following Total Knee Arthroplasty: The ABC Trial

Study Overview
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Brief Summary
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Rationale: Infection following total knee replacement (TKA) is a devastating complication that usually requires prosthesis removal, hospitalization while the infection is eradicated, and a second surgery to implant a revision prosthesis. For primary TKA, prophylactic antibiotic-loaded cement (ABC) may not only reduce the rate of infection it may also reduce the rate of revisions due to implant loosening. Current controversy about the use of ABC exists around the world. Without a definitive trial, patients will be exposed to a treatment of uncertain efficacy that may cause antibiotic resistant bacterial strains and will certainly generate high costs to the healthcare system. Purpose: To determine, 1) the extent to which ABC compared to regular cement reduces the infection rate in patients over the first two years following TKA and, 2) the resource use implications associated with the use of ABC for TKA. Methods: This is a randomized clinical trial in which 8,800 patients with undergoing primary TKA are allocated to either Simplex™ P with Tobramycin or Simplex™ P bone cement. We will exclude patients with a prior joint infection, an allergy to tobramycin, and those with no fixed address. All patients will be administered IV antibiotics immediately prior to surgery. Patients and surgeons will be blind to group allocation. The primary outcome measure is infection. Follow-up visits will take place at 6 weeks and 3, 12 and 24 months postoperative. A blinded adjudicator will review all reported infections and determine whether the putative infection is a study event. Blinded radiologists will interpret the 2 year series of radiographs for each patient. We will compare the rates of infection and implant loosening between the two treatment groups using survival analyses. This study includes a full economic analysis.

Official Title
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The Effectiveness of Antibiotic Cement Compared to Regular Cement in Reducing the Rate of Infection Following Total Knee Arthroplasty: The ABC Feasibility Study

Conditions
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Infection, Osteoarthritis of the Knee

Intervention / Treatment
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* Device: Simplex™ P with Tobramycin
* Device: Simplex™ P


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with osteoarthritis of the knee, patients who are undergoing primary knee replacement, patients who are able to provide informed consent. Exclusion Criteria: patients with a prior joint infection, patients who have a known allergy to tobramycin, and patients who have no fixed address.

Ages Eligible for Study
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Minimum Age: 18 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: Simplex™ P<br>All patients will receive preoperative antibiotics administered within the hour prior to surgery. All patients will undergo a cemented total knee replacement (both femoral and tibial components) with the type of implant left to the discretion of the surgeon. The patella may or may not be resurfaced depending on indication and preference. All patients will receive one of the two study cements (Simplex™ P with Tobramycin or Simplex™ P) in a blinded fashion; all cement vials will be similar in size and shape and the cement will be similar in odour, color and texture. No additional antibiotics will be added to the cement. Surgeons can use their preferred cement preparation technique (i.e. manual or vacuum mixing). The use of a suction drain will depend on surgical indication and preference. | Device: Simplex™ P<br>* All patients will receive preoperative antibiotics administered within the hour prior to surgery.All patients will undergo a cemented total knee replacement (both femoral and tibial components) with the type of implant left to the discretion of the surgeon. The patella may or may not be resurfaced depending on indication and preference. All patients will receive one of the two study cements (Simplex™ P with Tobramycin or Simplex™ P) in a blinded fashion; all cement vials will be similar in size and shape and the cement will be similar in odour, color and texture. No additional antibiotics will be added to the cement. Surgeons can use their preferred cement preparation technique (i.e. manual or vacuum mixing). The use of a suction drain will depend on surgical indication and preference.<br>|
| Experimental: Simplex™ P with Tobramycin<br>All patients will receive preoperative antibiotics administered within the hour prior to surgery.All patients will undergo a cemented total knee replacement (both femoral and tibial components) with the type of implant left to the discretion of the surgeon. The patella may or may not be resurfaced depending on indication and preference. All patients will receive one of the two study cements (Simplex™ P with Tobramycin or Simplex™ P) in a blinded fashion; all cement vials will be similar in size and shape and the cement will be similar in odour, color and texture. No additional antibiotics will be added to the cement. Surgeons can use their preferred cement preparation technique (i.e. manual or vacuum mixing). The use of a suction drain will depend on surgical indication and preference. | Device: Simplex™ P with Tobramycin<br>* All patients will receive preoperative antibiotics administered within the hour prior to surgery.All patients will undergo a cemented total knee replacement (both femoral and tibial components) with the type of implant left to the discretion of the surgeon. The patella may or may not be resurfaced depending on indication and preference. All patients will receive one of the two study cements (Simplex™ P with Tobramycin or Simplex™ P) in a blinded fashion; all cement vials will be similar in size and shape and the cement will be similar in odour, color and texture. No additional antibiotics will be added to the cement. Surgeons can use their preferred cement preparation technique (i.e. manual or vacuum mixing). The use of a suction drain will depend on surgical indication and preference.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relative risk of infection | patients suspected of having an infected total knee replacement in the post-operative period will be evaluated clinically, and will undergo lab evaluation and an aspiration | 6 weeks and 3, 12 and 24 months postoperative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| radiographic evidence of prosthetic failure |  | 6 weeks and 3, 12 and 24 months postoperative | 
| patient-reported disease-specific health-related quality of life (HRQOL) |  | 6 weeks and 3, 12 and 24 months postoperative | 
| cost-effectiveness |  | 6 weeks and 3, 12 and 24 months postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total knee arthroplasty, infection, antibiotic bone cement