Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection

NCT ID: NCT02365493

Last Updated: 2018-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-08-26

Study Completion Date

2018-10-24

Brief Summary

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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.

Detailed Description

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Conditions

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Methicillin-Resistant Staphylococcus Aureus

Keywords

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Methicillin-Resistant Staphylococcus aureus (MRSA)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type EXPERIMENTAL

Beta-Lactam

Intervention Type DRUG

Interventions

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Beta-Lactam

Intervention Type DRUG

Other Intervention Names

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flucloxacillin cloxacillin cephazolin

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Australasian Society for Infectious Diseases

OTHER

Sponsor Role collaborator

Singapore Infectious Diseases Clinical Research Network

OTHER

Sponsor Role collaborator

The University of Queensland

OTHER

Sponsor Role collaborator

Australasian Kidney Trials Network

NETWORK

Sponsor Role collaborator

Menzies School of Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joshua Davis, MBBS, FRACP

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Steven Tong, MBBS, FRACP

Role: PRINCIPAL_INVESTIGATOR

Menzies School of Health Research

Locations

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Blacktown Hospital

Blacktown, New South Wales, Australia

Site Status

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status

Concord Repatriation General Hospital

Concord, New South Wales, Australia

Site Status

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Site Status

Nepean Hospital

Kingswood, New South Wales, Australia

Site Status

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Wollongong Hospital

Wollongong, New South Wales, Australia

Site Status

Royal Darwin Hospital

Darwin, Northern Territory, Australia

Site Status

Cairns Hospital

Cairns, Queensland, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinder's Medical Centre

Bedford Park, South Australia, Australia

Site Status

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status

Monash Medical Centre Clayton Campus

Clayton, Victoria, Australia

Site Status

Dandenong Hospital

Dandenong, Victoria, Australia

Site Status

Western Health - Footscray

Footscray, Victoria, Australia

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Western Health - Sunshine Hospital

Sunshine, Victoria, Australia

Site Status

Western Health - Williamstown Hospital

Williamstown, Victoria, Australia

Site Status

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status

Royal Perth Hospital

Perth, Western Australia, Australia

Site Status

Rambam Health Corporation

Haifa, , Israel

Site Status

Beilinson Hospital

Petah Tikva, , Israel

Site Status

Middlemore Hospital

Otahuhu, Auckland, New Zealand

Site Status

Tan Tock Seng Hospital

Novena, Tan Tock Seng, Singapore

Site Status

National University Hospital

Kent Ridge, , Singapore

Site Status

Singapore General Hospital

Outram Park, , Singapore

Site Status

Countries

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Australia Israel New Zealand Singapore

References

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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.

Reference Type DERIVED
PMID: 32044943 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27029920 (View on PubMed)

Other Identifiers

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NHMRC1078930

Identifier Type: -

Identifier Source: org_study_id