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

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ClinicalTrials.gov Identifier: NCT02365493
Recruitment Status : Active, not recruiting
First Posted : February 19, 2015
Last Update Posted : August 16, 2018
Sponsor:
Collaborators:
Australasian Society for Infectious Diseases
Singapore Infectious Diseases Clinical Research Network
The University of Queensland
Australasian Kidney Trials Network
Information provided by (Responsible Party):
Menzies School of Health Research

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.


Condition or disease Intervention/treatment Phase
Methicillin-Resistant Staphylococcus Aureus Drug: Beta-Lactam Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 358 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: CAMERA 2 - Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection - An Investigator-initiated, Multi-centre, Parallel Group, Open Labelled Randomised Controlled Trial
Actual Study Start Date : August 26, 2015
Estimated Primary Completion Date : October 24, 2018
Estimated Study Completion Date : October 24, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics MRSA

Arm Intervention/treatment
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 (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.
Drug: Beta-Lactam
Other Names:
  • flucloxacillin
  • cloxacillin
  • cephazolin




Primary Outcome Measures :
  1. Complication-free 90 day survival [ Time Frame: 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 Outcome Measures :
  1. All-cause mortality at days 14, 42 and 90 days [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  2. Persistent bacteraemia at day 2 [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  3. Persistent bacteraemia at day 5 or beyond [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  4. 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 Frame: 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.

  5. Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  6. Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  7. Duration of intravenous antibiotic treatment [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  8. Direct health care costs [ Time Frame: Time period from randomisation (day 1) to day 90 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02365493


Locations
Australia, New South Wales
Blacktown Hospital
Blacktown, New South Wales, Australia, 2148
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia, 2050
Concord Repatriation General Hospital
Concord, New South Wales, Australia, 2139
St Vincent's Hospital
Darlinghurst, New South Wales, Australia, 2010
Nepean Hospital
Kingswood, New South Wales, Australia, 2747
Liverpool Hospital
Liverpool, New South Wales, Australia, 2170
John Hunter Hospital
New Lambton Heights, New South Wales, Australia, 2305
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Wollongong Hospital
Wollongong, New South Wales, Australia, 2500
Australia, Northern Territory
Royal Darwin Hospital
Darwin, Northern Territory, Australia, 0820
Australia, Queensland
Cairns Hospital
Cairns, Queensland, Australia, 4870
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia, 4029
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Flinder's Medical Centre
Bedford Park, South Australia, Australia, 5042
The Queen Elizabeth Hospital
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Monash Medical Centre Clayton Campus
Clayton, Victoria, Australia, 3168
Dandenong Hospital
Dandenong, Victoria, Australia, 3175
Western Health - Footscray
Footscray, Victoria, Australia, 3011
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Western Health - Sunshine Hospital
Sunshine, Victoria, Australia, 3021
Western Health - Williamstown Hospital
Williamstown, Victoria, Australia, 3016
Australia, Western Australia
Fiona Stanley Hospital
Murdoch, Western Australia, Australia, 6150
Royal Perth Hospital
Perth, Western Australia, Australia, 6000
Israel
Rambam Health Corporation
Haifa, Israel
Beilinson Hospital
Petah Tikva, Israel
New Zealand
Middlemore Hospital
Otahuhu, Auckland, New Zealand, 1640
Singapore
Tan Tock Seng Hospital
Novena, Tan Tock Seng, Singapore, 308433
National University Hospital
Kent Ridge, Singapore, 119074
Singapore General Hospital
Outram Park, Singapore, 168753
Sponsors and Collaborators
Menzies School of Health Research
Australasian Society for Infectious Diseases
Singapore Infectious Diseases Clinical Research Network
The University of Queensland
Australasian Kidney Trials Network
Investigators
Principal Investigator: Joshua Davis, MBBS, FRACP Menzies School of Health Research
Principal Investigator: Steven Tong, MBBS, FRACP Menzies School of Health Research

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT02365493     History of Changes
Other Study ID Numbers: NHMRC1078930
First Posted: February 19, 2015    Key Record Dates
Last Update Posted: August 16, 2018
Last Verified: August 2018

Keywords provided by Menzies School of Health Research:
Methicillin-Resistant Staphylococcus aureus (MRSA)

Additional relevant MeSH terms:
Staphylococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Cefazolin
Methicillin
Lactams
beta-Lactams
Cloxacillin
Floxacillin
Anti-Infective Agents