Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection (CAMERA2)

Menzies School of Health Research

Status and phase: Terminated; Phase 3

Conditions: Methicillin-Resistant Staphylococcus Aureus

Treatments: Drug: Beta-Lactam

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT02365493

NHMRC1078930

Details and patient eligibility

About

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.

Enrollment: 358 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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358 participants in 2 patient groups

Standard therapy

No Intervention group

Description:

Intravenous vancomycin dosed as per Australian Therapeutic Guidelines (loading dose of 25 mg/kg followed by maintenance dose of 15-20 mg/kg every 12 hours) with subsequent adjustment to maintain trough levels at 15-20 mg/dL OR Intravenous daptomycin 6-10 mg/kg per day, adjusted for renal function (details of renally adjusted dosing provided in full protocol). The choice of daptomycin or vancomycin is clinician-determined and may be influenced by such factors as local practice, the vancomycin minimum inhibitory concentration (MIC) of the isolate and evidence emerging during the course of the study

Standard therapy + Beta-Lactam

Experimental group

Description:

In addition to standard treatment an intravenous Beta-Lactam (β-lactam) will be added for the first 7 calendar days following randomisation (randomisation is day 1 - hence patients will receive 6-7 days of β-lactam). This β-lactam will be intravenous flucloxacillin 2g every 6 hours in Australia and intravenous cloxacillin 2g every 6 hours in Singapore. For those with a history of minor allergy to any penicillin (rash or unclear history, but not anaphylaxis or angiooedema), it will be intravenous cefazolin 2g every 8 hours. For haemodialysis patients, it will usually be cefazolin 2g three times per week post dialysis, however clinicians are also free to choose intermittent (flu)cloxacillin, dosed as for glomerular filtration rate (GFR ) \<10, if they desire.

Treatment:

Drug: Beta-Lactam