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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different durations of oral suppressive antibiotic therapy (SAT) for joint infections following surgery. Researchers will assess the impact of these antibiotics on patients, focusing on drug reactions, the need for additional surgery, and the potential for antibiotic resistance over time. The study includes three groups: one with indefinite SAT, another with 6 months, and the last with 12 months of therapy. Individuals who underwent surgery for a joint infection less than four weeks ago and have been on SAT for at least three months may qualify for this trial. As an unphased trial, it offers patients the chance to contribute to significant research that could enhance future treatment strategies.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that suppressive antibiotic therapy (SAT) for joint infections is generally well-tolerated by patients. One study found that patients on SAT for joint infections experienced few serious side effects, with the most common issues being mild, such as an upset stomach or diarrhea. Another study examined different doses of SAT and found that both low and normal doses were generally safe, with no major differences in side effects between them.

However, SAT is not a cure; it manages symptoms and delays further surgery. While SAT is generally safe, there is some concern about the risk of developing antibiotic resistance over time, meaning the bacteria causing the infection might stop responding to treatment. So far, these risks appear low based on existing studies.

Overall, SAT seems to be a safe option for managing joint infections after initial treatment. Regular check-ups with healthcare providers are crucial to monitor any side effects or changes in the infection. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for joint infections because they explore various durations of suppressive antibiotic therapy (SAT) following surgery and initial IV antibiotics. Unlike the typical course of antibiotics that might be used for a limited time, this trial investigates the potential benefits of indefinite or extended oral SAT, ranging from six months to a year. This approach could lead to more personalized treatment plans, potentially reducing recurrence rates and improving long-term outcomes for patients with joint infections. By examining different durations of SAT, researchers hope to identify the most effective strategy for preventing infection recurrence, offering new insights into managing these challenging infections.

What evidence suggests that this trial's treatments could be effective for joint infections?

This trial will compare different durations of suppressive antibiotic therapy (SAT) for managing infections in artificial joints. Research has shown that regular antibiotic use can help manage these infections. For instance, one study found that this approach reduced the need for additional surgeries after the initial treatment. Another study demonstrated that both low and regular doses of antibiotics effectively treated infections in joint implants. However, more research is needed to fully understand the best long-term use of antibiotics and to identify all associated benefits and risks. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 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 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 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]

Citations

1. journals.asm.org journals.asm.org/doi/10.1128/aac.01784-24

Outcomes after suppressive antimicrobial therapy for ... The objective of this study was to describe the use of and outcomes after suppressive antimicrobial therapy (SAT) in a large prospective peri-prosthetic joint ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11939255/

Suppressive Antibiotic Therapy in Prosthetic Joint Infections This study compared patients with orthopedic implant infections treated with low-dose versus normal-dose SAT, after an initial standard treatment of 1 to 2 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2352344125001761

Outcomes of Long-Term Antibiotic Therapy for Prosthetic ... Long-term antibiotic therapy (LAT) can be used to prevent relapse of prosthetic joint infection. Evidence on best practices for LAT is limited and ...

4. academic.oup.com academic.oup.com/cid/article/79/4/848/7687610

The Use of Long-term Antibiotics for Suppression of Bacterial ... In this narrative review we present the available evidence for the use of suppressive antibiotic therapy in 4 common indications.

5. journalofinfection.com journalofinfection.com/article/S0163-4453(24)00250-0/fulltext

Global practice variation of suppressive antimicrobial ... To identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8235685/

Suppressive Antibiotic Treatment in Prosthetic Joint Infections SAT is considered a “noncurative” strategy, in which antimicrobials are administered with the aim of reducing symptoms and delaying or preventing the ...

7. jbji.copernicus.org jbji.copernicus.org/articles/9/149/2024/jbji-9-149-2024.pdf

Dosing and treatment duration of suppressive antimicrobial ... Introduction: Limited data inform about the optimal dosing and duration of suppressive antimicro- bial therapy (SAT) for orthopedic implant ...