Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection

Methicillin-Resistant Staphylococcus Aureus Clinical Trial

— CAMERA2  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02365493
• Other study ID #: NHMRC1078930
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2015
• Est. completion date: October 24, 2018

Study information

• Verified date: December 2018
• Source: Menzies School of Health Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 358
• Est. completion date: October 24, 2018
• Est. primary completion date: October 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Methicillin-Resistant Staphylococcus Aureus
• Staphylococcal Infections

Intervention

Drug:
• Beta-Lactam

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Flinder's Medical Centre	Bedford Park	South Australia
Australia	Blacktown Hospital	Blacktown	New South Wales
Australia	Cairns Hospital	Cairns	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Medical Centre Clayton Campus	Clayton	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Dandenong Hospital	Dandenong	Victoria
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Royal Darwin Hospital	Darwin	Northern Territory
Australia	Western Health - Footscray	Footscray	Victoria
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	John Hunter Hospital	New Lambton Heights	New South Wales
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Western Health - Sunshine Hospital	Sunshine	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Western Health - Williamstown Hospital	Williamstown	Victoria
Australia	Wollongong Hospital	Wollongong	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville South	South Australia
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Israel	Rambam Health Corporation	Haifa
Israel	Beilinson Hospital	Petah Tikva
New Zealand	Middlemore Hospital	Otahuhu	Auckland
Singapore	National University Hospital	Kent Ridge
Singapore	Tan Tock Seng Hospital	Novena	Tan Tock Seng
Singapore	Singapore General Hospital	Outram Park

Sponsors (5)

Lead Sponsor	Collaborator
Menzies School of Health Research	Australasian Kidney Trials Network, Australasian Society for Infectious Diseases, Singapore Infectious Diseases Clinical Research Network, The University of Queensland

Countries where clinical trial is conducted

Australia,  Israel,  New Zealand,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complication-free 90 day survival	Composite outcome at 90 days - any of: All-cause mortality; Persistent bacteraemia at day 5 or beyond; Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture; Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation.	Time period from randomisation (day 1) to day 90
Secondary	All-cause mortality at days 14, 42 and 90 days		Time period from randomisation (day 1) to day 90
Secondary	Persistent bacteraemia at day 2		Time period from randomisation (day 1) to day 90
Secondary	Persistent bacteraemia at day 5 or beyond		Time period from randomisation (day 1) to day 90
Secondary	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.	Time period from randomisation (day 1) to day 90
Secondary	Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture		Time period from randomisation (day 1) to day 90
Secondary	Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation		Time period from randomisation (day 1) to day 90
Secondary	Duration of intravenous antibiotic treatment		Time period from randomisation (day 1) to day 90
Secondary	Direct health care costs		Time period from randomisation (day 1) to day 90