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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02365493




Registration number
NCT02365493
Ethics application status
Date submitted
11/02/2015
Date registered
19/02/2015
Date last updated
19/12/2018

Titles & IDs
Public title
Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection
Scientific title
CAMERA 2 - Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection - An Investigator-initiated, Multi-centre, Parallel Group, Open Labelled Randomised Controlled Trial
Secondary ID [1] 0 0
NHMRC1078930
Universal Trial Number (UTN)
Trial acronym
CAMERA2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methicillin-Resistant Staphylococcus Aureus 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Beta-Lactam

No Intervention: Standard therapy - 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

Experimental: Standard therapy + Beta-Lactam - In addition to standard treatment an intravenous Beta-Lactam (ß-lactam) will be added for the first 7 calendar days following randomisation (randomisation is day 1 - hence patients will receive 6-7 days of ß-lactam). This ß-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: Drugs: Beta-Lactam
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complication-free 90 day survival
Timepoint [1] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [1] 0 0
All-cause mortality at days 14, 42 and 90 days
Timepoint [1] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [2] 0 0
Persistent bacteraemia at day 2
Timepoint [2] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [3] 0 0
Persistent bacteraemia at day 5 or beyond
Timepoint [3] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [5] 0 0
Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture
Timepoint [5] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [6] 0 0
Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation
Timepoint [6] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [7] 0 0
Duration of intravenous antibiotic treatment
Timepoint [7] 0 0
Time period from randomisation (day 1) to day 90
Secondary outcome [8] 0 0
Direct health care costs
Timepoint [8] 0 0
Time period from randomisation (day 1) to day 90

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 ß-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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/08/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/10/2018
Sample size
Target
Accrual to date
Final
358
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [4] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [5] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [6] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [7] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [8] 0 0
Westmead Hospital - Westmead
Recruitment hospital [9] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [10] 0 0
Royal Darwin Hospital - Darwin
Recruitment hospital [11] 0 0
Cairns Hospital - Cairns
Recruitment hospital [12] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [13] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [14] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [15] 0 0
Flinder's Medical Centre - Bedford Park
Recruitment hospital [16] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [17] 0 0
Monash Medical Centre Clayton Campus - Clayton
Recruitment hospital [18] 0 0
Dandenong Hospital - Dandenong
Recruitment hospital [19] 0 0
Western Health - Footscray - Footscray
Recruitment hospital [20] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [21] 0 0
Western Health - Sunshine Hospital - Sunshine
Recruitment hospital [22] 0 0
Western Health - Williamstown Hospital - Williamstown
Recruitment hospital [23] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [24] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
2139 - Concord
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
2747 - Kingswood
Recruitment postcode(s) [6] 0 0
2170 - Liverpool
Recruitment postcode(s) [7] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [8] 0 0
2145 - Westmead
Recruitment postcode(s) [9] 0 0
2500 - Wollongong
Recruitment postcode(s) [10] 0 0
0820 - Darwin
Recruitment postcode(s) [11] 0 0
4870 - Cairns
Recruitment postcode(s) [12] 0 0
4029 - Herston
Recruitment postcode(s) [13] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [14] 0 0
5000 - Adelaide
Recruitment postcode(s) [15] 0 0
5042 - Bedford Park
Recruitment postcode(s) [16] 0 0
5011 - Woodville South
Recruitment postcode(s) [17] 0 0
3168 - Clayton
Recruitment postcode(s) [18] 0 0
3175 - Dandenong
Recruitment postcode(s) [19] 0 0
3011 - Footscray
Recruitment postcode(s) [20] 0 0
3084 - Heidelberg
Recruitment postcode(s) [21] 0 0
3021 - Sunshine
Recruitment postcode(s) [22] 0 0
3016 - Williamstown
Recruitment postcode(s) [23] 0 0
6150 - Murdoch
Recruitment postcode(s) [24] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Israel
State/province [1] 0 0
Haifa
Country [2] 0 0
Israel
State/province [2] 0 0
Petah Tikva
Country [3] 0 0
New Zealand
State/province [3] 0 0
Auckland
Country [4] 0 0
Singapore
State/province [4] 0 0
Tan Tock Seng
Country [5] 0 0
Singapore
State/province [5] 0 0
Kent Ridge
Country [6] 0 0
Singapore
State/province [6] 0 0
Outram Park

Funding & Sponsors
Primary sponsor type
Other
Name
Menzies School of Health Research
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Australasian Society for Infectious Diseases
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Singapore Infectious Diseases Clinical Research Network
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
The University of Queensland
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Australasian Kidney Trials Network
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02365493
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joshua Davis, MBBS, FRACP
Address 0 0
Menzies School of Health Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02365493