Methicillin-Resistant Staphylococcus Aureus
Conditions
Keywords
Methicillin-Resistant Staphylococcus aureus (MRSA)
Brief summary
The aim of this clinical trial is to determine whether a novel combination antibiotic treatment (vancomycin/daptomycin + beta-lactam) is superior to the standard antibiotic treatment (vancomycin/daptomycin) for hospitalised adults with Methicillin Resistant Staphylococcus aureus bacteraemia. The hypothesis is that the addition of beta-lactam antibiotics (these are antibiotics from the penicillin family) to the standard therapy will lead to more efficient bacterial killing and hence lead to faster clearance of bacteria from the blood stream and other areas of infection, thereby reducing the risk of the spread of infection and death. The study design is an investigator-initiated, multi-centre, open-label, randomised controlled trial. This will include 440 participants diagnosed with Methicillin Resistant Staphylococcus aureus bacteraemia recruited over a period of 4 years (July 2015 - June 2019) from within Infectious Diseases inpatient units across 21 hospital sites including 18 from within Australia and 3 located in Singapore. Participation will be voluntary and subject to informed consent. The participants will be randomised 1:1 to either the standard therapy group or combination therapy group. The combination therapy will include a treatment of intravenous beta-lactam for the first 7 days of treatment, in addition to the standard treatment (either vancomycin or daptomycin). The primary outcome measure will be complication-free survival 90 days post randomisation.
Interventions
DRUGBeta-Lactam
Sponsors
Australasian Society for Infectious Diseases
Singapore Infectious Diseases Clinical Research Network
The University of Queensland
Australasian Kidney Trials Network
Menzies School of Health Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>= 18 years. 2. ≥1 set of blood cultures positive for MRSA 3. Able to be randomized within 72 hours of blood cultures being collected. 4. Likely to remain as inpatient for 7 days following randomization
Exclusion criteria
1. Previous type 1 hypersensitivity reaction to ß-lactams 2. Polymicrobial bacteraemia (not counting contaminants) 3. Previous participation in the trial 4. Known pregnancy 5. Current β-lactam antibiotic therapy which cannot be ceased or substituted 6. Participant's primary clinician unwilling to enrol patient 7. Moribund (expected to die in next 48 hours with or without treatment) 8. Treatment limitations which preclude the use of antibiotics Note that we are NOT planning to exclude participants with renal failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complication-free 90 day survival | Time period from randomisation (day 1) to day 90 | Composite outcome at 90 days - any of: 1. All-cause mortality 2. Persistent bacteraemia at day 5 or beyond 3. Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture 4. Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality at days 14, 42 and 90 days | Time period from randomisation (day 1) to day 90 | — |
| Persistent bacteraemia at day 2 | Time period from randomisation (day 1) to day 90 | — |
| Persistent bacteraemia at day 5 or beyond | Time period from randomisation (day 1) to day 90 | — |
| Acute kidney injury defined as ≥ stage 1 modified RIFLE criteria at any time within the first 7 days, OR new need for renal replacement therapy at any time from days 1 to 90. Excludes participants already on haemodialysis. | Time period from randomisation (day 1) to day 90 | \>=stage 1 modified RIFLE criteria (1.5-fold increase in the serum creatinine, or glomerular filtration rate (GFR) decrease by 25 percent). This endpoint does not apply to participants who were already on haemodialysis at randomisation. |
| Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture | Time period from randomisation (day 1) to day 90 | — |
| Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation | Time period from randomisation (day 1) to day 90 | — |
| Duration of intravenous antibiotic treatment | Time period from randomisation (day 1) to day 90 | — |
| Direct health care costs | Time period from randomisation (day 1) to day 90 | — |
Countries
Australia, Israel, New Zealand, Singapore
Outcome results
None listed