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Methicillin-Resistant Staphylococcus AureusPhase 3CAMERA2NCT02365493

Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection

A Phase 3 study testing Beta-Lactam in people with Methicillin-Resistant Staphylococcus Aureus, run by Menzies School of Health Research at 30 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Beta-Lactam
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
358 participants
Where
30 sitesin 4 countries
Study dates
26 Aug 2015to 24 Oct 2018
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years.
  • ≥1 set of blood cultures positive for MRSA
  • Able to be randomized within 72 hours of blood cultures being collected.
  • Likely to remain as inpatient for 7 days following randomization

Who cannot join

  • Previous type 1 hypersensitivity reaction to ß-lactams
  • Polymicrobial bacteraemia (not counting contaminants)
  • Previous participation in the trial
  • Known pregnancy
  • Current β-lactam antibiotic therapy which cannot be ceased or substituted
  • Participant's primary clinician unwilling to enrol patient
  • Moribund (expected to die in next 48 hours with or without treatment)
  • Treatment limitations which preclude the use of antibiotics Note that we are NOT planning to exclude participants with renal failure.

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

Australia24 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Flinder's Medical Centre

    Bedford Park, South Australia, 5042

  • Blacktown Hospital

    Blacktown, New South Wales, 2148

  • Cairns Hospital

    Cairns, Queensland, 4870

  • Royal Prince Alfred Hospital

    Camperdown, New South Wales, 2050

  • Monash Medical Centre Clayton Campus

    Clayton, Victoria, 3168

  • Concord Repatriation General Hospital

    Concord, New South Wales, 2139

  • Dandenong Hospital

    Dandenong, Victoria, 3175

  • St Vincent's Hospital

    Darlinghurst, New South Wales, 2010

  • Royal Darwin Hospital

    Darwin, Northern Territory, 0820

  • Western Health - Footscray

    Footscray, Victoria, 3011

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Brisbane and Women's Hospital

    Herston, Queensland, 4029

  • Nepean Hospital

    Kingswood, New South Wales, 2747

  • Liverpool Hospital

    Liverpool, New South Wales, 2170

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • John Hunter Hospital

    New Lambton Heights, New South Wales, 2305

  • Royal Perth Hospital

    Perth, Western Australia, 6000

  • Western Health - Sunshine Hospital

    Sunshine, Victoria, 3021

  • Westmead Hospital

    Westmead, New South Wales, 2145

  • Western Health - Williamstown Hospital

    Williamstown, Victoria, 3016

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

  • The Queen Elizabeth Hospital

    Woodville South, South Australia, 5011

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Singapore3 sites

  • National University Hospital

    Kent Ridge, 119074

  • Tan Tock Seng Hospital

    Novena, Tan Tock Seng, 308433

  • Singapore General Hospital

    Outram Park, 168753

Other trials in Singapore

Israel2 sites

  • Rambam Health Corporation

    Haifa

  • Beilinson Hospital

    Petah Tikva

Other trials in Israel

New Zealand1 site

  • Middlemore Hospital

    Otahuhu, Auckland, 1640

Other trials in New Zealand

About this study

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

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.

Being tested
Beta-Lactam
Keywords
Methicillin-Resistant Staphylococcus aureus (MRSA)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Beta-LactamDrug

    Also called flucloxacillin, cloxacillin, cephazolin

Study groups in NCT02365493
Study groupRoleWhat they receive
Standard therapyNo interventionIntravenous 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-LactamExperimentalIn 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.
Receives: Drug: Beta-Lactam

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complication-free 90 day survival

    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.

    Measured: Time period from randomisation (day 1) to day 90

Secondary outcomes (8)

  1. All-cause mortality at days 14, 42 and 90 days

    Measured: Time period from randomisation (day 1) to day 90

  2. Persistent bacteraemia at day 2

    Measured: Time period from randomisation (day 1) to day 90

  3. Persistent bacteraemia at day 5 or beyond

    Measured: 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.

    >=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.

    Measured: Time period from randomisation (day 1) to day 90

  5. Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture

    Measured: 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

    Measured: Time period from randomisation (day 1) to day 90

  7. Duration of intravenous antibiotic treatment

    Measured: Time period from randomisation (day 1) to day 90

  8. Direct health care costs

    Measured: Time period from randomisation (day 1) to day 90

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2015 (estimated)
  2. Study start26 Aug 2015
  3. Primary completion24 Oct 2018
  4. Study completion24 Oct 2018

Why it stopped: Recommendation of the Data Safety Monitoring Committee

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
358 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02365493
Sponsor's protocol ID
NHMRC1078930
Acronym
CAMERA2
Status last verified
Dec 2018
First submitted
11 Feb 2015
Last updated
19 Dec 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Tong SYC, Lye DC, Yahav D, Sud A, Robinson JO, Nelson J, Archuleta S, Roberts MA, Cass A, Paterson DL, Foo H, Paul M, Guy SD, Tramontana AR, Walls GB, McBride S, Bak N, Ghosh N, Rogers BA, Ralph AP, Davies J, Ferguson PE, Dotel R, McKew GL, Gray TJ, Holmes NE, Smith S, Warner MS, Kalimuddin S, Young BE, Runnegar N, Andresen DN, Anagnostou NA, Johnson SA, Chatfield MD, Cheng AC, Fowler VG Jr, Howden BP, Meagher N, Price DJ, van Hal SJ, O'Sullivan MVN, Davis JS; Australasian Society for Infectious Diseases Clinical Research Network. Effect of Vancomycin or Daptomycin With vs Without an Antistaphylococcal beta-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients With MRSA Bacteremia: A Randomized Clinical Trial. JAMA. 2020 Feb 11;323(6):527-537. doi: 10.1001/jama.2020.0103.

    PubMed 32044943

  • Tong SY, Nelson J, Paterson DL, Fowler VG Jr, Howden BP, Cheng AC, Chatfield M, Lipman J, Van Hal S, O'Sullivan M, Robinson JO, Yahav D, Lye D, Davis JS; CAMERA2 study group and the Australasian Society for Infectious Diseases Clinical Research Network. CAMERA2 - combination antibiotic therapy for methicillin-resistant Staphylococcus aureus infection: study protocol for a randomised controlled trial. Trials. 2016 Mar 31;17:170. doi: 10.1186/s13063-016-1295-3.

    PubMed 27029920

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Beta-Lactam in people with Methicillin-Resistant Staphylococcus Aureus, run by Menzies School of Health Research at 30 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in Australia, Singapore, Israel, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Recommendation of the Data Safety Monitoring Committee). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complication-free 90 day survival (time frame: Time period from randomisation (day 1) to day 90). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02365493, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2018.

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