Prosthetic Valve Endocarditis, Staphylococcus Aureus Endocarditis
Conditions
Keywords
S. aureus bacteremia, Prosthetic valve endocarditis, Rifampin
Brief 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.
Interventions
DRUGRifampin
Patients will receive rifampin 900mg a day in 2-3 divided doses
OTHERNo rifampin
Subjects will be assigned to not receive adjunctive rifampin
Sponsors
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
Todd C. Lee MD MPH FIDSA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The trial analyst will also be blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment failure | 180 days | A composite outcome of all cause mortality, unplanned cardiac surgery, new cardioembolic events, or relapse of bacteremia due to S. aureus. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | 180 days | Death due to any cause |
| Unplanned cardiac surgery | 180 days | The need for cardiac surgery which was not planned or scheduled at the time of randomization. |
| New embolic events | 180 days | A new symptomatic cardio-embolic event occurring after randomization. |
| Discontinuation of rifampin due to new drug-drug interaction | 56 days | The cessation of adjunctive rifampin due to a new pharmacologically significant drug-drug interaction. |
| Serious adverse drug reaction due to rifampin | 56 days | Patients who have a CTCAE grade 4 reaction which is determined by expert adjudication to be probably or definitely due to rifampin. |
| Discontinuation of rifampin due to an adverse drug reaction | 56 days | Any adverse drug reaction which leads to the discontinuation of rifampin |
| Relapse of bacteremia | 180 days | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Development of rifampin resistant S. aureus | 180 days | Any clinically relevant isolate of S. aureus which demonstrates resistance to rifampin. |
Countries
Canada
Contacts
Primary ContactLina Petrella
Outcome results
None listed