Clinical trial NCT02365493: Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Methicillin-Resistant Staphylococcus Aureus
Keywords: Methicillin-Resistant Staphylococcus aureus (MRSA)
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
Collaborators: name: Australasian Society for Infectious Diseases
name: Singapore Infectious Diseases Clinical Research Network
name: The University of Queensland
name: Australasian Kidney Trials Network
First posted: 2015-02-19
Enrollment: 358
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Complication-free 90 day survival
timeFrame: Time period from randomisation (day 1) to day 90
Secondary outcomes:
measure: All-cause mortality at days 14, 42 and 90 days
timeFrame: Time period from randomisation (day 1) to day 90
measure: Persistent bacteraemia at day 2
timeFrame: Time period from randomisation (day 1) to day 90
measure: Persistent bacteraemia at day 5 or beyond
timeFrame: Time period from randomisation (day 1) to day 90
measure: 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.
timeFrame: Time period from randomisation (day 1) to day 90
measure: Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture
timeFrame: Time period from randomisation (day 1) to day 90
measure: Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation
timeFrame: Time period from randomisation (day 1) to day 90
measure: Duration of intravenous antibiotic treatment
timeFrame: Time period from randomisation (day 1) to day 90
measure: Direct health care costs
timeFrame: Time period from randomisation (day 1) to day 90
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Liverpool Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Wollongong Hospital
state: New South Wales
city: Darwin
country: Australia
facility: Royal Darwin Hospital
state: Northern Territory
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinder's Medical Centre
state: South Australia
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton Campus
state: Victoria
city: Dandenong
country: Australia
facility: Dandenong Hospital
state: Victoria
city: Footscray
country: Australia
facility: Western Health - Footscray
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Sunshine
country: Australia
facility: Western Health - Sunshine Hospital
state: Victoria
city: Williamstown
country: Australia
facility: Western Health - Williamstown Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Haifa
country: Israel
facility: Rambam Health Corporation
city: Petah Tikva
country: Israel
facility: Beilinson Hospital
city: Otahuhu
country: New Zealand
facility: Middlemore Hospital
state: Auckland
city: Novena
country: Singapore
facility: Tan Tock Seng Hospital
state: Tan Tock Seng
city: Kent Ridge
country: Singapore
facility: National University Hospital
city: Outram Park
country: Singapore
facility: Singapore General Hospital
Study officials:
affiliation: Menzies School of Health Research
name: Joshua Davis, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Menzies School of Health Research
name: Steven Tong, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.