Proper Duration of Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention

Study Overview
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Brief Summary
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Multiple studies have demonstrated oral suppressive antibiotic therapy (SAT), after intravenous antibiotics, maximizes reoperation-free survival of total joint arthroplasty (TJA) debridement, antibiotics, and implant retention (DAIR) for acute periprosthetic joint infection (PJI). However, little is known regarding sequelae of SAT after DAIR for PJI. Prior studies have small or heterogeneous patient cohorts, variable antibiotic regimens, arrive at disparate conclusions, and do not establish antibiotic resistance risk. The investigators propose a prospective randomized controlled multicenter study to expand on findings in a retrospective, multi-center pilot study. Study aims are to evaluate SAT after DAIR of acutely infected primary TJA regarding: 1) adverse drug reactions/intolerance; 2) reoperation for infection; and 3) antibiotic resistance.

Official Title
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Randomized Clinical Trial Determining Proper Duration of Suppressive Antibiotic Therapy After Total Joint Arthroplasty Debridement, Antibiotics, and Implant Retention

Conditions
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Periprosthetic Joint Infection, Antibiotic Suppression

Intervention / Treatment
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* Drug: 6 months of SAT
* Drug: 12 months of SAT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: over 18 years-old underwent DAIR with modular component exchange for acute TJA PJI, as defined by Musculoskeletal Infection Society Criteria, with symptom duration less than 4 weeks on postoperative oral SAT for at least 3 months Exclusion Criteria: underwent aseptic revision surgery had one-stage, 1.5-stage, or two-stage revision surgery did not have postoperative SAT did not have follow-up that allowed for evaluation of SAT sequelae

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 6 months of SAT<br>TJA DAIR, followed by 6 weeks of IV antibiotics then 6 months of oral suppressive antibiotic therapy | Drug: 6 months of SAT<br>* 6 months of oral suppressive antibiotic therapy<br>|
| Active Comparator: 12 months of SAT<br>TJA DAIR, followed by 6 weeks of IV antibiotics then 12 months of oral suppressive antibiotic therapy | Drug: 12 months of SAT<br>* 12 months of oral suppressive antibiotic therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reoperation for infection recurrence |  | 2 years after study initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibiotic resistance, evidenced by change in antimicrobial sensitivity profile, developed by infecting organism after suppressive antibiotic therapy causing infection recurrence |  | at time of reoperation (within 2 years of study initiation) | 
| Adverse drug reaction or intolerance, defined as any symptom or laboratory value derangement requiring a change in, or discontinuation of, antimicrobial therapy | Antibiotic intolerance is any Grade I sign from CTCAE v5.0, while adverse drug reaction is any Grade 2 sign or higher. | 1 year after study initiation (during antibiotic administration) |