Antibiotics for Joint Infections

(ProperSAT Trial)

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must be taking: Suppressive antibiotics

Disqualifiers: Aseptic revision, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks for IV antibiotics, followed by varying durations of oral SAT

438 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves taking oral suppressive antibiotic therapy, it's best to discuss your current medications with the trial team to ensure there are no interactions.

What data supports the effectiveness of the treatment for joint infections?

Research shows that using suppressive antibiotic therapy (SAT) for at least 3 months can increase the chances of successfully treating orthopedic hardware infections, including joint infections, especially when surgery is not an option. ^{1 2 3 4 5}

Is suppressive antibiotic therapy (SAT) safe for treating joint infections?

Research indicates that suppressive antibiotic therapy (SAT) for joint infections is generally well-tolerated, with studies showing it does not commonly lead to adverse drug reactions or antibiotic resistance. ^{1 2 4 6 7}

How does suppressive antibiotic treatment differ from other treatments for joint infections?

Suppressive antibiotic treatment (SAT) is unique because it involves the long-term use of antibiotics to control joint infections when surgery is not an option or is unlikely to succeed. Unlike curative treatments, SAT aims to manage the infection rather than eliminate it, making it a valuable option for patients with complex cases or those who cannot undergo surgery. ^{1 2 4 8 9}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for adults over 18 who had a specific surgery (DAIR with modular component exchange) for an acute joint infection after a total joint arthroplasty, with symptoms lasting less than 4 weeks. They must have been on oral antibiotics post-surgery for at least 3 months.

Inclusion Criteria

I am over 18 years old.

I had surgery for a joint infection within 4 weeks of symptoms starting.

I have been taking oral hormone therapy for at least 3 months after surgery.

Exclusion Criteria

I had surgery to fix a previous operation without infection.

Patients who did not have follow-up that allowed for evaluation of SAT sequelae

I did not receive SAT after surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo TJA DAIR, followed by 6 weeks of IV antibiotics and then oral suppressive antibiotic therapy

6 weeks for IV antibiotics, followed by varying durations of oral SAT

Follow-up

Participants are monitored for adverse drug reactions, reoperation for infection, and antibiotic resistance

Up to 2 years

Treatment Details

Interventions

• SAT

Trial Overview The study tests how long to give suppressive antibiotic therapy (SAT) after the DAIR procedure: indefinitely, for 6 months, or for 12 months. It aims to see which duration minimizes complications like drug reactions and reoperations due to infections while also considering antibiotic resistance.

Participant Groups

Group I: Indefinite SAT Active Control 1 Intervention

TJA DAIR, followed by 6 weeks of IV antibiotics then indefinite oral suppressive antibiotic therapy

Group II: 6 months of SAT Active Control 1 Intervention

TJA DAIR, followed by 6 weeks of IV antibiotics then 6 months of oral suppressive antibiotic therapy

Group III: 12 months of SAT Active Control 1 Intervention

TJA DAIR, followed by 6 weeks of IV antibiotics then 12 months of oral suppressive antibiotic therapy

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

New England Baptist Hospital

Collaborator

Trials

1

Recruited

440+

OrthoMichigan

Collaborator

Trials

1

Recruited

440+

NYU School of Medicine

Collaborator

Trials

3

Recruited

1,200+

Sinai Hospital

Collaborator

Trials

1

Recruited

440+

MedStar Georgetown

Collaborator

Trials

3

Recruited

5,500+

NYU Grossman School of Medicine

Collaborator

Trials

5

Recruited

2,400+

MedStar Health

Collaborator

Trials

9

Recruited

76,100+

The New England Baptist Hospital

Collaborator

Trials

10

Recruited

3,100+

OrthoCarolina Research Institute, Inc.

Collaborator

Trials

37

Recruited

6,000+

Findings from Research

Suppressive antibiotic treatment (SAT) is becoming an important option for patients with prosthetic joint infections (PJIs) when curative surgery is not feasible or has a low success rate.

Recent studies over the last five years have provided new insights into SAT, highlighting its relevance as life expectancy increases and more orthopedic surgeries are performed, necessitating a better understanding of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective. Cobo, J., Escudero-Sanchez, R.[2021]

In a study of 302 patients with prosthetic joint infections (PJI) who could not undergo surgery, suppressive antibiotic treatment (SAT) was successful in controlling the infection in 58.6% of cases over a median duration of 36.5 months.

Factors associated with SAT failure included being younger than 70 years, having an infection caused by organisms other than Gram-positive cocci, and having the prosthesis located in the upper limb, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study. Escudero-Sanchez, R., Senneville, E., Digumber, M., et al.[2020]

In a study of 89 patients with orthopedic hardware infections, using oral suppressive antibiotics for at least 3 months after diagnosis was associated with a higher likelihood of being free from clinical infection after one year.

However, using suppressive antibiotics for 6 months did not show a significant benefit, and the type of bacteria causing the infection, particularly methicillin-resistant Staphylococcus aureus and Gram-negative rods, negatively impacted treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Suppressive Oral Antibiotics in Orthopedic Hardware Infections for Those Not Undergoing Two-Stage Replacement Surgery. Keller, SC., Cosgrove, SE., Higgins, Y., et al.[2023]

In a study of 51 patients with intravascular device-related infections who were not eligible for surgery, long-term suppressive antimicrobial therapy was found to be effective in preventing signs of infection relapse, with only 7.32% experiencing a relapse during treatment.

The therapy was generally well-tolerated, although some patients experienced adverse drug events, indicating that while effective, monitoring for side effects is important in long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term suppressive antimicrobial therapy for intravascular device-related infections. Baddour, LM.[2019]

In a study of 45 patients undergoing total joint arthroplasty (TJA) while on long-term oral suppressive antibiotic therapy (SAT), the rate of peri-prosthetic joint infection (PJI) was found to be 2.22%, which was not significantly different from the 1.11% rate in a matched control group of 180 patients.

The findings suggest that oral SAT does not increase the risk of PJI in patients undergoing primary TJA, indicating that SAT may be a safe option for these patients, although further large-scale studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peri-Prosthetic Joint Infection in Patients Prescribed Suppressive Antibiotic Therapy Undergoing Primary Total Joint Arthroplasty: A 1:4 Case Control Matched Study. Humphrey, TJ., Dunahoe, JA., Nelson, SB., et al.[2022]

Suppressive antibiotic therapy (SAT) after debridement, antibiotics, and implant retention (DAIR) for joint infections significantly improves reoperation-free survival, with no cases of antibiotic resistance reported during the study of 115 patients over a median SAT duration of 11 months.

However, caution is advised when prescribing trimethoprim/sulfamethoxazole, as it was associated with a higher risk of adverse drug reactions (11.1% for TKA and 16.3% for THA patients).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention is Well-Tolerated Without Inducing Resistance: A Multicenter Study. Nandi, S., Doub, JB., De Palma, BJ., et al.[2023]

The review highlights the uncertainty surrounding the optimal treatment for prosthetic joint infection (PJI) and emphasizes the need for identifying patients at the highest risk of treatment failure after debridement, antibiotics, and implant retention (DAIR) to determine who may benefit most from suppressive antibiotic therapy (SAT).

Current literature suggests that while SAT may help reduce treatment failure rates after DAIR, the evidence is limited, and there are concerns about adverse events that could lead to treatment discontinuation, necessitating careful risk-benefit analysis for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How we approach suppressive antibiotic therapy (SAT) following debridement, antibiotics, and implant retention for prosthetic joint infection. Cortes-Penfield, N., Krsak, M., Damioli, L., et al.[2023]

In a study of 20 patients with chronic osteomyelitis who received prolonged oral antibiotic suppression, 60% achieved successful disease suppression for an average of 778 days after stopping treatment.

Diabetic patients were found to be at a higher risk for treatment failure (p = 0.0281), and there was a notable 25% rate of adverse drug reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged oral antibiotic suppression in osteomyelitis and associated outcomes in a Veterans population. Nowak, MA., Winner, JS., Beilke, MA.[2019]

In a study of 78 patients with periprosthetic joint infections (PJIs), oral cyclines (doxycycline and minocycline) were found to have acceptable tolerability and effectiveness as suppressive antibiotic therapy, with only 18% reporting adverse events.

After an average follow-up of about 3 years, 28.2% of patients experienced treatment failure, indicating that while cyclines can be effective, there is a risk of developing antibiotic resistance in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. Pradier, M., Robineau, O., Boucher, A., et al.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Suppressive Antibiotic Treatment in Prosthetic Joint Infections: A Perspective. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy in prosthetic joint infections: a multicentre cohort study. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Role of Suppressive Oral Antibiotics in Orthopedic Hardware Infections for Those Not Undergoing Two-Stage Replacement Surgery. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Long-term suppressive antimicrobial therapy for intravascular device-related infections. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Peri-Prosthetic Joint Infection in Patients Prescribed Suppressive Antibiotic Therapy Undergoing Primary Total Joint Arthroplasty: A 1:4 Case Control Matched Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention is Well-Tolerated Without Inducing Resistance: A Multicenter Study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

How we approach suppressive antibiotic therapy (SAT) following debridement, antibiotics, and implant retention for prosthetic joint infection. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Prolonged oral antibiotic suppression in osteomyelitis and associated outcomes in a Veterans population. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. [2018]