Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000940077
Ethics application status
Approved
Date submitted
12/10/2010
Date registered
4/11/2010
Date last updated
25/08/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
CAMERA - Combination Antibiotic treatment for Methicillin Resistant Staphylococcus Aureus
Scientific title
In adults with methicillin resistant staphylococcus aureus (MRSA) bacteraemia, does the combination of vancomycin plus flucloxacillin lead to a faster resolution of bacteraemia than does vancomycin alone?
Secondary ID [1] 252858 0
N/A
Universal Trial Number (UTN)
Trial acronym
CAMERA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Methicillin Resistant Staphylococcus Aureus Bacteraemia 258571 0
Condition category
Condition code
Infection 258713 258713 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Vancomycin 1.5 grams every 12 hours infused intravenously over 90 minutes (for standard duration of 2-6 weeks) PLUS flucloxacillin 2grams every six hours infused intravenously over 10-30 minutes (for 7 days). Both Vancomycin and Flucloxacillin will be comenced on day one. The duration of Vancomycin treatment will be decided by the treating clinician based on clinical variables and response.
Intervention code [1] 257543 0
Treatment: Drugs
Comparator / control treatment
Vancomycin 1.5 grams every 12 hours infused intravenously over 90 minutes (for standard duration of 2-6 weeks). The duration of Vancomycin treatment will be decided by the treating clinician based on clinical variables and response.
Control group
Active

Outcomes
Primary outcome [1] 259393 0
Duration of MRSA bacteraemia. Blood culutres will be collected daily for the first 7 days and, if still postitive at day 7, every 48 hours therafter until negative. A negative blood culture means no growth detected in an automated blood culture system after 48 hours of incubation.
Timepoint [1] 259393 0
Blood cultures will be collected daily for the first 7 days and, if still postitive at day 7, every 48 hours therafter until negative. A negative blood culture means no growth detected in an automated blood culture system after 48 hours of incubation.
Secondary outcome [1] 265927 0
Clinical cure, as judged by an infectious diseases physician. Clinical cure is defined as resolution of fever for more than 48 hours, resolution of all clinical signs of infection, no longer receving any antibiotic treatment for the index infection, and at least one negative blood culutre after the cessation of all antibiotics.
Timepoint [1] 265927 0
90 days post randomisation
Secondary outcome [2] 265928 0
All-cause mortality as determined from hospital discharge data. If the patient is discharged from hospital prior to 28 days post randomisation, they or their general practitioner will be contacted to determine their vital status.
Timepoint [2] 265928 0
28 days post randomisation
Secondary outcome [3] 265929 0
Composite endpoint of development of new renal impairment or WHO grade 2 or higher abnormal liver enzymes. New renal impairment is defined as serum creatinine>1.5 times the upper limit of normal if it was <=1.25 upper limit of normal at trial entry; WHO Grade 2 or higher liver toxicity is defined as one or both of alanine transaminase or gamma glutaryl tranferase of >2.6 times the upper limit of normal
Timepoint [3] 265929 0
First 10 days following randomisation

Eligibility
Key inclusion criteria
1. MRSA identified in a blood culture drawn within 48 hours prior to randomisation
2. Hospital inpatient with expected stay of at least 7 days
Minimum age
18 Years
Maximum age
100 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Definite history of allergy to vancomycin or flucloxacillin
2. Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30ml/min
3. Polymicrobial bacteraemia in the index MRSA blood culture
4. Current treatment with a beta-lactam antibiotic which the patient's clinician deems necessary to continue
5. Pregnancy
6. Previous randomisation into this study

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)
Following written informed consent, the patient will be randomised by sequentially numbered opaque sealed envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified by centre. Randomisation in permuted blocks of variable block size.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Pilot study to determine feasibility and inform design of a larger study with mortality as the primary endpoint. Main aim is to determine the duration of bacteraemia in the treatment and control groups, rather than to demonstrate efficacy.
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
22/11/2010
Actual
12/01/2011
Date of last participant enrolment
Anticipated
Actual
6/05/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,WA
Recruitment postcode(s) [1] 3302 0
0811

Funding & Sponsors
Funding source category [1] 257826 0
Government body
Name [1] 257826 0
Northern Territory Research and Innovation Board
Address [1] 257826 0
Ground Floor
Development House
76 The Esplanade
Darwin NT 0800
Country [1] 257826 0
Australia
Primary sponsor type
Individual
Name
Dr Joshua Davis
Address
Menzies School of Health Research
Rocklands Drive
Tiwi
NT 0811
Country
Australia
Secondary sponsor category [1] 257027 0
Individual
Name [1] 257027 0
Dr Steven Tong
Address [1] 257027 0
Menzies School of Health Research
Rocklands Drive
Tiwi
NT 0811
Country [1] 257027 0
Australia
Other collaborator category [1] 251556 0
Other Collaborative groups
Name [1] 251556 0
Australian Society for Infectious Diseases Clinical Research Network
Address [1] 251556 0
C/- The Royal Australasian College of Physicians
145 Macquarie Street
Sydney, NSW 2000
AUSTRALIA
Country [1] 251556 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259856 0
Human Research Ethics Committee of the Menzies School of Health Research and Northern Territory Department of Health and Families
Ethics committee address [1] 259856 0
Menzies School of Health Research
Rocklands Drive
Tiwi
NT 0811
Ethics committee country [1] 259856 0
Australia
Date submitted for ethics approval [1] 259856 0
15/07/2010
Approval date [1] 259856 0
12/10/2010
Ethics approval number [1] 259856 0
1/10/1436

Summary
Brief summary
MRSA bacteraemia has a mortality of 30-40%, exceeding that of sensitive Staphylococcus aureus primarily due to the shortcomings of vancomycin, the standard therapy for MRSA bacteraemia. Whilst several new antibiotics have become available for MRSA, none have been shown to be superior to vancomycin. Although MRSA is by definition resistant to oxacillin, multiple in-vitro and animal studies have demonstrated synergy of vancomycin with beta-lactams (including oxacillin) against MRSA and hetro-resistant vancomycin intermediate Staphylococcus aureus (hVISA). This study aims to answer the following question: In hospitalised adults with MRSA bacteraemia, does combination therapy with vancomycin and flucloxacillin lead to a shorter time to clearance of bacteraemia than vancomycin alone?
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31761 0
Dr Josh Davis
Address 31761 0
Menzies School of Health Research Rocklands Drive Tiwi NT 0811
Country 31761 0
Australia
Phone 31761 0
+61 8 89448005
Fax 31761 0
Email 31761 0
Joshua.Davis@menzies.edu.au
Contact person for public queries
Name 15008 0
Dr Dr Josh Davis
Address 15008 0
Menzies School of Health Research
Rocklands Drive
Tiwi NT 0811
Country 15008 0
Australia
Phone 15008 0
+61 8 89448005
Fax 15008 0
Email 15008 0
Joshua.Davis@menzies.edu.au
Contact person for scientific queries
Name 5936 0
Dr Dr Josh Davis
Address 5936 0
Menzies School of Health Research
Rocklands Drive
Tiwi NT 0811
Country 5936 0
Australia
Phone 5936 0
+61 8 89448005
Fax 5936 0
Email 5936 0
Joshua.Davis@menzies.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary