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

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

This is a sub-study of the S. aureus Network Adaptive Platform (SNAP) trial (NCT05137119) wherein we will evaluate whether not giving rifampin in patients with probable or definite prosthetic valve endocarditis due to S. aureus is non-inferior to giving rifampin.

Study Overview

• Status: Recruiting
• Conditions: Staphylococcus Aureus Endocarditis; Prosthetic Valve Endocarditis
• Intervention / Treatment: Other: No rifampin; Drug: Rifampin

• Study Type: Interventional
• Enrollment (Estimated): 330
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Lina Petrella; Phone Number: 23730 514-934-1934; Email: lina.petrella@affiliate.mcgill.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A4S1
      • Recruiting
      • McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital)
      • Principal Investigator: Emily G McDonald, MD MSc
      • Principal Investigator: Todd C Lee, MD MPH FIDSA
      • Contact: Lina Petrella; Phone Number: 23730 15149341934; Email: todd.lee@mcgill.ca
      • Sub-Investigator: Matthew P. Cheng, MD MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No rifampin; These patients will not receive adjunctive rifampin.	Other: No rifampin; Subjects will be assigned to not receive adjunctive rifampin
Active Comparator: Adjunctive rifampin; These patients will receive adjunctive rifampin as recommended in guidelines.	Drug: Rifampin; Patients will receive rifampin 900mg a day in 2-3 divided doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure	A composite outcome of all cause mortality, unplanned cardiac surgery, new cardioembolic events, or relapse of bacteremia due to S. aureus.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Death due to any cause	180 days
Unplanned cardiac surgery	The need for cardiac surgery which was not planned or scheduled at the time of randomization.	180 days
New embolic events	A new symptomatic cardio-embolic event occurring after randomization.	180 days
Relapse of bacteremia	A new S. aureus bacteremia with the same susceptibility pattern (except for quinolones or rifampin in those who are exposed) which develops after sterilization of the initial blood cultures	180 days
Discontinuation of rifampin due to new drug-drug interaction	The cessation of adjunctive rifampin due to a new pharmacologically significant drug-drug interaction.	56 days
Serious adverse drug reaction due to rifampin	Patients who have a CTCAE grade 4 reaction which is determined by expert adjudication to be probably or definitely due to rifampin.	56 days
Discontinuation of rifampin due to an adverse drug reaction	Any adverse drug reaction which leads to the discontinuation of rifampin	56 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of rifampin resistant S. aureus	Any clinically relevant isolate of S. aureus which demonstrates resistance to rifampin.	180 days

Collaborators and Investigators

• Sponsor: Todd C. Lee MD MPH FIDSA
• Collaborators: Canadian Institutes of Health Research (CIHR); McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Melbourne; The Peter Doherty Institute for Infection and Immunity

Publications and helpful links

General Publications

• Ryder JH, Tong SYC, Gallagher JC, McDonald EG, Thevarajan I, Lee TC, Cortes-Penfield NW. Deconstructing the Dogma: Systematic Literature Review and Meta-analysis of Adjunctive Gentamicin and Rifampin in Staphylococcal Prosthetic Valve Endocarditis. Open Forum Infect Dis. 2022 Oct 31;9(11):ofac583. doi: 10.1093/ofid/ofac583. eCollection 2022 Nov.
• McDonald EG, Aggrey G, Aslan AT, Casias M, Cortes-Penfield N, Dong MQD, Egbert S, Footer B, Isler B, King M, Maximos M, Wuerz TC, Azim AA, Alza-Arcila J, Bai AD, Blyth M, Boyles T, Caceres J, Clark D, Davar K, Denholm JT, Forrest G, Ghanem B, Hagel S, Hanretty A, Hamilton F, Jent P, Kang M, Kludjian G, Lahey T, Lapin J, Lee R, Li T, Mehta D, Moore J, Mowrer C, Ouellet G, Reece R, Ryder JH, Sanctuaire A, Sanders JM, Stoner BJ, So JM, Tessier JF, Tirupathi R, Tong SYC, Wald-Dickler N, Yassin A, Yen C, Spellberg B, Lee TC. Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement. JAMA Netw Open. 2023 Jul 3;6(7):e2326366. doi: 10.1001/jamanetworkopen.2023.26366.

Helpful Links

• Main Website for the S. aureus Network Adaptive Platform Trial (SNAP)

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: November 19, 2025
• First Posted (Estimated): November 28, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Rifampin; S. aureus bacteremia; Prosthetic valve endocarditis
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Rifampin
• Other Study ID Numbers: 2025-10882

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing policies are dependent on the policies of the SNAP Platform (NCT05137119)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No