Staphylococcus Aureus EndocarditisPhase 3RIFA-SNAPNCT07253688
Adjunctive Rifampin for the Treatment of Prosthetic Valve Endocarditis Due to S. Aureus
A Phase 3 study testing Rifampin and No rifampin in people with Staphylococcus Aureus Endocarditis and Prosthetic Valve Endocarditis, run by Todd C. Lee MD MPH FIDSA at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Staphylococcus Aureus Endocarditis, Prosthetic Valve Endocarditis
- What is being tested?
- Rifampin and No rifampin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteCanada
- Study dates
- 10 Nov 2025to 14 Sep 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
- Patient or healthcare proxy provide informed consent.
Who cannot join
- Death deemed imminent and inevitable within days or patient will be receiving palliative care and has prognosis < 90 days according to the treating team;
- Patient requires intensive care but has a do not resuscitate order precluding transfer;
- Polymicrobial bacteremia (not including skin commensals or other recognized contaminant);
- Organism tests as rifampin resistant;
- History of hypersensitivity/anaphylaxis or severe adverse reaction to rifampin;
- 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];
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- Child Pugh Class C cirrhosis;
- Clinician deems rifampin to be mandatory;
- Patient has already received >3 days of rifampin at time of screening or >10 days of total therapy
- Pregnancy or breast feeding
- Administrative exclusions:
- No reliable means of outpatient contact (telephone/email/text);
- Previously enrolled;
- Prior S. aureus bacteremia within the preceding 180 days
Trial locations and contacts
1 site in 1 country.
Canada1 site
McGill University Health Centre (Royal Victoria Hospital and Montreal General Hospital)
Montreal, Quebec, H4A4S1
About this study
Official title: 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.
- Being tested
- Rifampin, No rifampin
- Keywords
- S. aureus bacteremia, Prosthetic valve endocarditis, Rifampin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RifampinDrug
Patients will receive rifampin 900mg a day in 2-3 divided doses
No rifampinOther
Subjects will be assigned to not receive adjunctive rifampin
| Study group | Role | What they receive |
|---|---|---|
| No rifampin | Experimental | These patients will not receive adjunctive rifampin. Receives: Other: No rifampin |
| Adjunctive rifampin | Active comparator | These patients will receive adjunctive rifampin as recommended in guidelines. Receives: Drug: Rifampin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment failure
A composite outcome of all cause mortality, unplanned cardiac surgery, new cardioembolic events, or relapse of bacteremia due to S. aureus.
Measured: 180 days
Secondary outcomes (7)
All-cause mortality
Death due to any cause
Measured: 180 days
Unplanned cardiac surgery
The need for cardiac surgery which was not planned or scheduled at the time of randomization.
Measured: 180 days
New embolic events
A new symptomatic cardio-embolic event occurring after randomization.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 56 days
Discontinuation of rifampin due to an adverse drug reaction
Any adverse drug reaction which leads to the discontinuation of rifampin
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2025
- Study start10 Nov 2025
- Primary completion14 Sep 2026
- Study completion14 Sep 2026
Why it stopped: After reviewing the recruitment to date as well as considering the anticipated ongoing recruitment challenges and feasibility, the decision was made to close the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Staphylococcus Aureus EndocarditisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Todd C. Lee MD MPH FIDSA
- Sponsor type
- University, hospital or other
- Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre, Canadian Institutes of Health Research (CIHR), University of Melbourne, The Peter Doherty Institute for Infection and Immunity
- Responsible party
- Sponsor-investigator, Todd C. Lee MD MPH FIDSA, McGill University Health Centre/Research Institute of the McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07253688
- Sponsor's protocol ID
- 2025-10882
- Other IDs
- 2025
- Acronym
- RIFA-SNAP
- Status last verified
- Sep 2026
- First submitted
- 19 Nov 2025
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Data sharing policies are dependent on the policies of the SNAP Platform (NCT05137119)
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.
PubMed 36408468McDonald 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.
PubMed 37523190
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Rifampin for the Treatment of Prosthetic Valve Endocarditis Due to S. Aureus (RIFA-SNAP)
- ClinicalTrials.gov ID
- NCT07253688
- Acronym / sponsor ID
- RIFA-SNAP / 2025-10882
- Keywords
- S. aureus bacteremia, Prosthetic valve endocarditis, Rifampin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: After reviewing the recruitment to date as well as considering the anticipated ongoing recruitment challenges and feasibility, the decision was made to close the study.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Todd C. Lee MD MPH FIDSAUniversity, hospital or other
- Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre, Canadian Institutes of Health Research (CIHR), University of Melbourne, The Peter Doherty Institute for Infection and Immunity
- Study start
- 10 Nov 2025 (actual)
- Primary completion
- 14 Sep 2026 (actual)
- Study completion
- 14 Sep 2026 (actual)
- First posted
- 28 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No rifampin | Experimental | Other: No rifampinThese patients will not receive adjunctive rifampin. |
| Adjunctive rifampin | Active comparator | Drug: RifampinThese patients will receive adjunctive rifampin as recommended in guidelines. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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);
- Patient or healthcare proxy provide informed consent.
Key exclusion criteria (14 listed)
- Death deemed imminent and inevitable within days or patient will be receiving palliative care and has prognosis < 90 days according to the treating team;
- Patient requires intensive care but has a do not resuscitate order precluding transfer;
- Polymicrobial bacteremia (not including skin commensals or other recognized contaminant);
- Organism tests as rifampin resistant;
- History of hypersensitivity/anaphylaxis or severe adverse reaction to rifampin;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RifampinPatients will receive rifampin 900mg a day in 2-3 divided doses | Drug | Adjunctive rifampin |
| No rifampinSubjects will be assigned to not receive adjunctive rifampin | Other | No rifampin |
Primary outcome
Treatment failure
Time frame: 180 days
A composite outcome of all cause mortality, unplanned cardiac surgery, new cardioembolic events, or relapse of bacteremia due to S. aureus.
7 secondary outcomes
All-cause mortality
Time frame: 180 days
Unplanned cardiac surgery
Time frame: 180 days
New embolic events
Time frame: 180 days
Relapse of bacteremia
Time frame: 180 days
Discontinuation of rifampin due to new drug-drug interaction
Time frame: 56 days
Serious adverse drug reaction due to rifampin
Time frame: 56 days
Discontinuation of rifampin due to an adverse drug reaction
Time frame: 56 days
Results and safety
The study was stopped early (reason given: After reviewing the recruitment to date as well as considering the anticipated ongoing recruitment challenges and feasibility, the decision was made to close the study.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Background: PubMed 36408468Ryder 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.
- Background: PubMed 37523190McDonald 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.
- Main Website for the S. aureus Network Adaptive Platform Trial (SNAP)Link provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Data sharing policies are dependent on the policies of the SNAP Platform (NCT05137119)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rifampin and No rifampin in people with Staphylococcus Aureus Endocarditis and Prosthetic Valve Endocarditis, run by Todd C. Lee MD MPH FIDSA at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: After reviewing the recruitment to date as well as considering the anticipated ongoing recruitment challenges and feasibility, the decision was made to close the study.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment failure (time frame: 180 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07253688, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.