Staphylococcus Aureus Bacteremia
Conditions
Keywords
Methicillin-resistant Staphylococcus aureus (MRSA), Methicillin-susceptible Staphylococcus aureus (MSSA), Penicillin-susceptible Staphylococcus aureus (PSSA), Staphylococcus aureus, S. aureus, Staph Aureus Bacteremia (SAB)
Brief summary
The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is an International Multi-Centered Randomised Adaptive Platform Clinical Trial to evaluate a range of interventions to reduce mortality for patients with Staphylococcus Aureus bacteraemia (SAB).
Detailed description
Infection of the bloodstream with the bacterium Staphylococcus aureus (Staphylococcus aureus bacteraemia, SAB) is a serious infection that results in 15-30% of affected patients dying within three months of acquiring the infection. Treatment of this infection requires patients to be hospitalised, treated with prolonged antibiotics through an intravenous line, and carefully examined for the occurrence of complications associated with this condition. At present, there are many treatment options in current use, with no clear agreement as to which of these is best. The SNAP trial aims to identify which treatment options for SAB results in the fewest patients dying within the first 90 days after an infection. In contrast to a conventional clinical trial, the SNAP trial will examine multiple different treatment options at once. Patients will be randomly assigned to different concurrent treatment options currently considered acceptable in routine medical care, but as the trial progresses, more patients will be assigned to treatments that appear to have better outcomes than those with worse outcomes. The trial will adapt to accumulating trial evidence, on a regular basis, by removing treatment options found to be inferior, incorporating new treatment options, and ensuring that all patients in the trial receive the best treatments once they have been identified. Over time, we hope to determine the best combination of treatment options for patients with SAB. The SNAP Trial infrastructure will also support a number of sub-studies. A list of all active sub-studies can be found on the SNAP website: https://www.snaptrial.com.au/substudies.
Interventions
DRUGCefazolin
Cefazolin
DRUGPenicillin
benzylpenicillin
DRUGClindamycin
Clindamycin
DRUGVancomycin
Vancomycin or Daptomycin
OTHEREffectiveness of early switch to oral antibiotics
This involves testing a strategy rather than individual antibiotic agents
RADIATIONWhole body FDG PET/CT Imaging
Whole body FDG PET/CT imaging will be performed using a standardised protocol describing patient preparation and minimum specifications for radiopharmaceutical production, quality control, and PET/CT acquisition.
Sponsors
Berry Consultants
McGill University Health Centre/Research Institute of the McGill University Health Centre
Menzies School of Health Research
Aotearoa Clinical Trials
Queensland University of Technology
Sunnybrook Health Sciences Centre
Tan Tock Seng Hospital
Telethon Kids Institute
The Peter Doherty Institute for Infection and Immunity
The University of Queensland
UMC Utrecht
Radboud University Medical Center
King's College London
Rambam Health Care Campus
University College, London
The Methodist Hospital Research Institute
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study
Intervention model description
Participants enrolled into the study have the option of deciding whether to be randomised in one or more (if available) treatment domains concurrently, if they meet the eligibility criteria.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
PLATFORM Inclusion Criteria: Patients must fulfil all of the following criteria to be eligible to enter the SNAP trial: 1. Staphylococcus aureus complex grown from ≥1 blood culture 2. Admitted to a participating hospital at the time of eligibility assessment (OR if patient has died, they were admitted to this site anytime from the time of blood culture collection until the time of eligibility assessment) PLATFORM
Exclusion criteria
Potentially eligible participants meeting any of the following criteria at the time of eligibility assessment for platform entry will be excluded from the randomised platform (but may still participate in the registry): 1. Time of anticipated platform entry is greater than 72 hours post collection of the index blood culture (Where the time of culture collection is not recorded, the time of laboratory registration of the sample will be used as an alternative) 2. Polymicrobial bacteraemia, defined as more than one organism (at species level) in the index blood cultures OR in any subsequent blood culture reported between the collection of the index blood culture and platform eligibility assessment, excluding those organisms judged to be contaminants by either the microbiology laboratory or treating clinician. 3. Known previous participation in the randomised SNAP platform 4. Known positive blood culture for S. aureus (of the same silo: PSSA, MSSA or MRSA) between 72 hours and 180 days prior to the time of eligibility assessment 5. Treating team deems enrolment in the study is not in the best interest of the patient 6. Treating team believes that death is imminent and inevitable 7. Patient is for end-of-life care and antibiotic treatment is considered not appropriate 8. Patient \<18 years of age and paediatric recruitment not approved at recruiting site 9. Patient has died since the collection of the index blood culture To be included in any of the following DOMAINS the participant must met eligible for the PLATFORM (as listed above) ADJUNCTIVE TREATMENT DOMAIN Inclusion Criteria: 1. All participants that met the PLATFORM eligible are eligible to be included in this domain unless they meet any of the following exclusions listed. 2. Patients are eligible for this domain regardless of S. aureus susceptibility testing results to clindamycin.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality at 90 days after platform entry | From randomisation (day 1) until day 90 | The primary endpoint for all cells and domains will be all-cause mortality at 90 days after platform entry. The primary endpoint will be determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core2: Duration of survival censored at 90 days after platform entry | From randomisation (day 1) until day 90 | Determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries. |
| Core3: Length of stay of acute index inpatient hospitalisation for those surviving until discharge from acute inpatient facilities (excluding HITH/COPAT/OPAT/rehab). | From randomisation (day 1) until discharge from acute inpatient facilities, truncated at 90 days. | Acute index hospitalisation is defined as continuous hospital admission to one or more acute inpatient facilities for the index episode. This does not include HITH/OPAT/COPAT and stepdown inpatient rehabilitation/post-acute care. It does include admission to acute care hospitals immediately preceding and following those at the enrolling site. |
| Core4: Length of stay of total index hospitalisation for those surviving until hospital discharge (including HITH/COPAT/OPAT/rehab) | From randomisation (day 1) to discharge from total index hospitalisation, truncated at 90 days | Total index hospitalisation is defined as continuous hospital admission to one or more inpatient facilities for the index episode, including HITH/OPAT/COPAT and stepdown inpatient rehabilitation/post-acute care (if continuous with the initial inpatient admission). It includes admission to acute care hospitals immediately preceding and following those at the enrolling site. |
| Core5: Time to being discharged alive from the total index hospitalisation (including HITH/COPAT/OPAT/rehab) truncated at 90 days after platform entry | From randomisation (day 1) to discharge from total index hospitalisation, truncated at 90 days | and all deaths within 90 days will be considered '90 days' |
| Core6: Microbiological treatment failure defined as positive sterile site culture for S. aureus [of the same silo as the index isolate between 14 and 90 days after platform entry). | From day 14 until day 90 | A sterile site means any sites deep to the skin and skin structures, including deep visceral and musculoskeletal abscesses that have been obtained in a sterile manner. |
| Core7: Diagnosis of new foci between 14 and 90 days after platform entry. | From day 14 until day 90 | The presence of new foci will be determined by the site investigator and can incorporate clinical, radiological, microbiological and pathological findings. |
| Core8: C. difficile diarrhoea as determined by a clinical laboratory in the 90 days following platform entry for participants ≥2 years of age. | From randomisation (day 1) until day 90 | This means a stool submitted to a clinical laboratory has tested positive for C. difficile toxin or toxin gene. |
| Core1: All-cause mortality at 14, 28 and 42 days after platform entry | From randomisation (day 1) until day 14, 28, and 42 | Determined through a search of hospital databases for a record of a participant's death, or follow-up contact with the participant's community healthcare provider, or follow-up contact with the patient or their nominated carer, or linkage with death registries. |
| Core10: Health economic costs as detailed in the health ecnomics appendix. | From randomisation (day 1) until day 90 | Including hospital length of stay, readmissions, and patient employment status. |
| Core11: Proportion of participants who have returned to their usual level of function at day 90. | From randomisation (day 1) until day 90 | Determined by whether the modified functional bloodstream infection score (FBIS) remained the same or improved between baseline and 90 days after platform entry where baseline=best score within the 4 weeks prior to platform entry. |
| Core12: Desirability of outcome ranking 1 (DOOR1; modified Antibiotic Resistance Leadership Group version) | From randomisation (day 1) until day 90 | See Core Protocol; unable to insert DOOR1 table |
| Core13: Desirability of outcome ranking 2 (DOOR2; SNAP version) | From randomisation (day 1) until day 90 | See Core Protocol; unable to insert DOOR2 table |
| Core14: Total number of antibiotic days (IV and/or oral/enteral) in the 90 days following platform entry. | From randomisation (day 1) until day 90 | All antibiotics should be included, not only those intended for treatment of S. aureus bacteraemia. It also includes prophylactic dose antibiotics (e.g., prophylactic dose trimethoprim-sulfamethoxazole). All days on which any antibiotic dose is received should be counted - i.e. we are counting the number of whole or part days on which any antibiotics are received (not the number of defined daily doses of antibiotics). Topical, inhaled or other routes of administration besides IV or oral/enteral should not be counted. |
| Core15: Days alive and free of antibiotics in the 90 days following platform entry. | From randomisation (day 1) until day 90 | All antibiotics should be included, not only those intended for treatment of S. aureus bacteraemia. It also includes prophylactic dose antibiotics (e.g., prophylactic dose trimethoprim-sulfamethoxazole). All days on which any antibiotic dose is received should be counted - i.e. we are counting the number of whole or part days on which any antibiotics are received (not the number of defined daily doses of antibiotics). Topical, inhaled or other routes of administration besides IV or oral/enteral should not be counted. |
| Core9: Serious adverse reactions (SARs) in the 90 days following platform entry | From randomisation (day 1) until day 90 | SARs defined only as serious events that are attributable to one or more randomised study interventions |
Countries
Australia, Canada, Israel, Japan, Netherlands, New Zealand, Singapore, South Africa, United Kingdom, United States
Contacts
Primary ContactLauren Barina
Backup ContactSusan Goulding
Outcome results
None listed