Rifampin added or omitted for Staphylococcus aureus infection of a prosthetic heart valve.

Adjunctive Rifampin for the Treatment of Prosthetic Valve Endocarditis Due to S. Aureus (RIFA-SNAP)

This test will see if skipping rifampin works as well as giving rifampin for people with probable or definite Staphylococcus aureus infection of a prosthetic heart valve.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 330 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (Academic / other)
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT07253688 on ClinicalTrials.gov

What this trial studies

This is a sub-study embedded within the SNAP adaptive platform that focuses on patients with probable or definite prosthetic valve endocarditis due to Staphylococcus aureus according to the 2023 Duke-ISCVID criteria. Eligible participants are randomized to receive adjunctive rifampin or no rifampin alongside standard antibiotic therapy. The trial is designed as a non-inferiority comparison to determine whether omission of rifampin yields similar clinical outcomes. Clinical endpoints and safety (including relapse, complications, and adverse events) are followed during hospitalization and subsequent clinical follow-up.

Who should consider this trial

Good fit: Adults with probable or definite prosthetic valve endocarditis caused by Staphylococcus aureus who can give informed consent and do not have rifampin resistance or other contraindications.

Not a fit: Patients with rifampin-resistant organisms, polymicrobial bacteremia, unmanageable drug–drug interactions, or a very limited life expectancy are unlikely to benefit from this comparison.

Why it matters

Potential benefit: If successful, patients could avoid rifampin's drug interactions and side effects while receiving equally effective treatment.

How similar studies have performed: Rifampin is commonly used in clinical practice for prosthetic valve infections but randomized evidence is limited, so this randomized non-inferiority comparison is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Probable or definite prosthetic valve endocarditis involving the tricuspid, pulmonic, mitral and/or aortic valves by the 2023 Duke-ISCVID Criteria (including Cardiac PET evidence if applicable);
2. Patient or healthcare proxy provide informed consent.

Exclusion Criteria:

1. Death deemed imminent and inevitable within days or patient will be receiving palliative care and has prognosis \< 90 days according to the treating team;
2. Patient requires intensive care but has a do not resuscitate order precluding transfer;
3. Polymicrobial bacteremia (not including skin commensals or other recognized contaminant);
4. Organism tests as rifampin resistant;
5. History of hypersensitivity/anaphylaxis or severe adverse reaction to rifampin;
6. Category X or other important drug-drug interaction with rifampin which cannot be safely mitigated \[with as-needed consultation from experts from pharmacy and/or internal medicine/geriatrics for potential deprescribing\];
7. Child Pugh Class C cirrhosis;
8. Clinician deems rifampin to be mandatory;
9. Patient has already received \>3 days of rifampin at time of screening or \>10 days of total therapy
10. Pregnancy or breast feeding

Administrative exclusions:

1. No reliable means of outpatient contact (telephone/email/text);
2. Previously enrolled;
3. Prior S. aureus bacteremia within the preceding 180 days

Where this trial is running

Montreal, Quebec

• McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital) — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Study coordinator: Lina Petrella

Conditions Staphylococcus Aureus Endocarditis; Prosthetic Valve Endocarditis; S. aureus bacteremia; Prosthetic valve endocarditis; Rifampin