Rifampin for Valve Infection

(RIFA-SNAP Trial)

Overseen By Lina Petrella

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Todd C. Lee MD MPH FIDSA

Must not be taking: Rifampin

Disqualifiers: Rifampin resistance, Child Pugh C, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether omitting the antibiotic rifampin is as effective as including it in treating heart valve infections caused by Staphylococcus aureus. Participants will either receive rifampin with their standard treatment or not receive rifampin at all. The trial seeks to determine if excluding rifampin can still effectively treat the infection without compromising results. Individuals with a confirmed or likely infection of an artificial heart valve with Staphylococcus aureus might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but if you are taking any drugs that interact with rifampin, you may need to adjust them. It's best to discuss your medications with the trial team.

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

Research has shown that rifampin, a common antibiotic, is often recommended for treating infections of the heart valve, specifically staphylococcal prosthetic valve endocarditis. However, caution is advised when adding rifampin to other standard treatments. Some studies suggest that rifampin does not significantly improve survival rates or reduce the chance of infection recurrence compared to treatments without it. Other studies found similar patient outcomes regardless of rifampin use.

These findings indicate that while rifampin is widely used, its safety and effectiveness can vary. It is generally well-tolerated, but like any medication, it can cause side effects, such as liver problems or allergic reactions, though these are uncommon. Overall, evidence suggests that rifampin is safe for most people, but its benefits might not be as clear as once thought. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Rifampin is unique because it offers an adjunctive approach to treating valve infections, a condition typically managed with standard antibiotics like vancomycin or gentamicin. Most treatments for valve infections focus on directly killing the bacteria. However, rifampin works differently by penetrating biofilms that bacteria use to protect themselves, enhancing the effectiveness of other antibiotics. Researchers are excited about rifampin's potential to improve outcomes by targeting these biofilms, potentially leading to quicker and more effective infection control.

What evidence suggests that this trial's treatments could be effective for prosthetic valve endocarditis?

In this trial, participants will divide into two groups: one will receive adjunctive rifampin, while the other will not. Research has shown that using rifampin to treat prosthetic valve infections caused by Staphylococcus aureus bacteria doesn't always improve outcomes. One study found that survival and relapse rates after one year were similar regardless of rifampin use. Another study noted that while rifampin was sometimes used, it was linked to more cases of increased liver enzymes, indicating liver stress or damage. Overall, the benefits of adding rifampin to standard treatment remain under investigation, and its effectiveness in this context is not clearly proven. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with a heart valve infection caused by S. aureus bacteria, specifically those with probable or definite prosthetic valve endocarditis. Participants must consent to the study and not have any conditions that require rifampin as mandatory treatment, no severe reactions to rifampin, no multi-bacterial infections, and not be pregnant or breastfeeding.

Inclusion Criteria

Patient or healthcare proxy provide informed consent

I have an infection in my heart valve replacement confirmed by specific criteria.

Exclusion Criteria

Clinician deems rifampin to be mandatory

Polymicrobial bacteremia (not including skin commensals or other recognized contaminant)

History of hypersensitivity/anaphylaxis or severe adverse reaction to rifampin

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjunctive rifampin or no rifampin for the treatment of prosthetic valve endocarditis due to S. aureus

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

180 days

What Are the Treatments Tested in This Trial?

Interventions

• Rifampin

Trial Overview The study is testing if not using the antibiotic rifampin in patients with prosthetic valve endocarditis due to S. aureus is just as effective as using it. It's part of a larger SNAP trial comparing these two approaches.

How Is the Trial Designed?

Group I: No rifampin Experimental Treatment 1 Intervention

These patients will not receive adjunctive rifampin.

Group II: Adjunctive rifampin Active Control 1 Intervention

These patients will receive adjunctive rifampin as recommended in guidelines.

Who Is Running the Clinical Trial?

Todd C. Lee MD MPH FIDSA

Lead Sponsor

Trials

3

Recruited

660+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

University of Melbourne

Collaborator

Trials

193

Recruited

1,287,000+

The Peter Doherty Institute for Infection and Immunity

Collaborator

Trials

18

Recruited

15,300+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32706879/

Is Rifampin Use Associated With Better Outcome in ... Conclusions: A large proportion (43.9%) of staphylococcal PVE received no rifampin. One-year survival and relapse rates were similar in patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213716524001929

Clinical reality for adjunctive rifampin usage in infective ... A total of 59 patients used RBC during treatment. The median duration of rifampin treatment in these patients was 34.5(2-200) days. 28 of these patients were ...

3. ahajournals.org ahajournals.org/doi/10.1161/circ.144.suppl_1.10302

Abstract 10302: A Case for Ending Rifampicin Use in ... The primary endpoint was all-cause death, while relapse, bail-out valvular surgery, microbiological failure (lasting positivity of blood ...

4. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(24)00089-2/pdf

Should Rifampin Be Used to Treat Staphylococcal ... RIFAMPIN FOR STAPHYLOCOCCAL PROSTHETIC VALVE ENDOCARDITIS. Mayo Clin Proc ... Is rifampin use associated with better outcome in staphylococcal prosthetic valve ...

5. journals.asm.org journals.asm.org/doi/10.1128/aac.00300-08

Addition of Rifampin to Standard Therapy for Treatment of ... Cases who received rifampin were more likely to have elevated hepatic transaminases (n = 9) than were controls (n = 1) (P = 0.014); this result occurred only ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2443910/

Addition of Rifampin to Standard Therapy for Treatment of ... Our results suggest that adding rifampin to standard antibiotic therapy for the treatment of native valve S. aureus IE should be done with caution, especially ...

7. academic.oup.com academic.oup.com/cid/article-abstract/72/9/e249/5876044

Is Rifampin Use Associated With Better Outcome in ... One-year survival and relapse rates were similar in patients treated with or without rifampin. Topic: prosthetic valve endocarditis; cerebral embolism ...