We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified April 2017 by Menzies School of Health Research
Sponsor:
ClinicalTrials.gov Identifier:
NCT02365493
First Posted: February 19, 2015
Last Update Posted: April 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
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
  Purpose

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 Intervention Phase
Methicillin-Resistant Staphylococcus Aureus Drug: Beta-Lactam Phase 3

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Menzies School of Health Research:

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

  • 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 ]
  • 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 ]
  • Duration of intravenous antibiotic treatment [ Time Frame: Time period from randomisation (day 1) to day 90 ]
  • Direct health care costs [ Time Frame: Time period from randomisation (day 1) to day 90 ]

Estimated Enrollment: 440
Study Start Date: August 2015
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
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


Contacts
Contact: Joshua Davis, MBBS, FRACP +61488191938 joshua.davis@menzies.edu.au
Contact: Steven Tong, MBBS, FRACP +618 89228928 steven.tong@menzies.edu.au

Locations
Australia, New South Wales
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Adrian Ong         
Principal Investigator: Adrian Ong         
Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Sebastian VanHal         
Principal Investigator: Sebastian VanHal         
Concord Repatriation General Hospital Recruiting
Concord, New South Wales, Australia, 2139
Contact: Genevieve McKew         
Principal Investigator: Genevieve McKew         
St Vincent's Hospital Recruiting
Darlinghurst, New South Wales, Australia, 2010
Contact: David Andresen         
Principal Investigator: David Andresen         
Nepean Hospital Recruiting
Kingswood, New South Wales, Australia, 2747
Contact: Archana Sud         
Principal Investigator: Archana Sud         
Liverpool Hospital Recruiting
Liverpool, New South Wales, Australia, 2170
Contact: Hong Foo         
Principal Investigator: Hong Foo         
John Hunter Hospital Recruiting
New Lambton Heights, New South Wales, Australia, 2305
Contact: Joshua Davis       joshua.davis@menzies.edu.au   
Principal Investigator: Joshua Davis         
Westmead Hospital Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Matthew O'Sullivan         
Principal Investigator: Matthew O'Sullivan         
Wollongong Hospital Recruiting
Wollongong, New South Wales, Australia, 2500
Contact: Niladri Ghosh         
Principal Investigator: Niladri Ghosh         
Australia, Northern Territory
Royal Darwin Hospital Recruiting
Darwin, Northern Territory, Australia, 0820
Contact: Steven Tong       steven.tong@menzies.edu.au   
Principal Investigator: Steven Tong         
Australia, Queensland
Cairns Hospital Recruiting
Cairns, Queensland, Australia, 4870
Contact: Simon Smith         
Contact: Josh Hanson         
Principal Investigator: Simon Smith         
Sub-Investigator: Josh Hanson         
Royal Brisbane and Women's Hospital Recruiting
Herston, Queensland, Australia, 4029
Contact: David Paterson         
Principal Investigator: David Paterson         
Princess Alexandra Hospital Recruiting
Woolloongabba, Queensland, Australia, 4102
Contact: Naomi Runnegar         
Principal Investigator: Naomi Runnegar         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Narin Bak         
Principal Investigator: Narin Bak         
The Queen Elizabeth Hospital Recruiting
Woodville South, South Australia, Australia, 5011
Contact: Morgyn Warner         
Principal Investigator: Morgyn Warner         
Australia, Victoria
Monash Medical Centre Clayton Campus Recruiting
Clayton, Victoria, Australia, 3168
Contact: Ben Rogers         
Principal Investigator: Ben Rogers         
Dandenong Hospital Recruiting
Dandenong, Victoria, Australia, 3175
Contact: Ben Rogers         
Principal Investigator: Ben Rogers         
Western Health - Footscray Recruiting
Footscray, Victoria, Australia, 3011
Contact: Stephen Guy         
Principal Investigator: Stephen Guy         
Sub-Investigator: Adrian Tramontana         
Austin Hospital Recruiting
Heidelberg, Victoria, Australia, 3084
Contact: Benjamin Howden         
Principal Investigator: Benjamin Howden         
Western Health - Sunshine Hospital Recruiting
Sunshine, Victoria, Australia, 3021
Contact: Stephen Guy         
Principal Investigator: Stephen Guy         
Sub-Investigator: Adrian Tramontana         
Western Health - Williamstown Hospital Recruiting
Williamstown, Victoria, Australia, 3016
Contact: Stephen Guy         
Principal Investigator: Stephen Guy         
Sub-Investigator: Adrian Tramontana         
Australia, Western Australia
Fiona Stanley Hospital Recruiting
Murdoch, Western Australia, Australia, 6150
Contact: Owen Robinson         
Principal Investigator: Owen Robinson         
Sub-Investigator: Paul Ingram         
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia, 6000
Contact: Owen Robinson         
Principal Investigator: Owen Robinson         
Sub-Investigator: Paul Ingram         
Israel
Rambam Health Corporation Recruiting
Haifa, Israel
Contact: Mical Paul         
Principal Investigator: Mical Paul         
Beilinson Hospital Recruiting
Petah Tikva, Israel
Contact: Dafna Yahav         
Principal Investigator: Dafna Yahav         
New Zealand
Middlemore Hospital Recruiting
Otahuhu, Auckland, New Zealand, 1640
Contact: Stephen McBride         
Contact: Genevieve Walls         
Principal Investigator: Stephen McBride         
Sub-Investigator: Genevieve Walls         
Singapore
Tan Tock Seng Hospital Recruiting
Novena, Tan Tock Seng, Singapore, 308433
Contact: David Lye         
Principal Investigator: David Lye         
National University Hospital Recruiting
Kent Ridge, Singapore, 119074
Contact: Sophia Archuleta         
Principal Investigator: Sophia Archuleta         
Singapore General Hospital Recruiting
Outram Park, Singapore, 168753
Contact: Tan Thuan Tong         
Principal Investigator: Tan Thuan Tong         
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
  More Information

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 Submitted: February 11, 2015
First Posted: February 19, 2015
Last Update Posted: April 17, 2017
Last Verified: April 2017

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