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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT02176122
Registration number
NCT02176122
Ethics application status
Date submitted
24/06/2014
Date registered
26/06/2014
Date last updated
27/11/2017
Titles & IDs
Public title
RCT Meropenem vs Piperacillin-Tazobactam for Definitive Treatment of BSI's Due to Ceftriaxone Non-susceptible Escherichia Coli and Klebsiella Spp.
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Scientific title
Randomized Controlled Trial of Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Due to Ceftriaxone Non-susceptible E. Coli and Klebsiella Species.
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Secondary ID [1]
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ACTRN12613000532707
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Universal Trial Number (UTN)
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Trial acronym
MERINO
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infections
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Condition category
Condition code
Infection
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Studies of infection and infectious agents
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Infection
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Other infectious diseases
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Inflammatory and Immune System
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Other inflammatory or immune system disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Meropenem
Treatment: Drugs - Piperacillin-tazobactam combination product
Active comparator: Meropenem - Meropenem 1g adm every 8 hours IV up to study day 4.
Experimental: Piperacillin-tazobactam combination product - Piperacillin/tazobactam 4.5g adm every 6 hours IV up to study day 4.
Treatment: Drugs: Meropenem
Meropenem is a carbapenem anti-bacterial used for the treatment of serious infections in patients.
Treatment: Drugs: Piperacillin-tazobactam combination product
Piperacillin-tazobactam is used for the treatment of patients with systemic and/or local bacterial infections.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Mortality at 30 days
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Assessment method [1]
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To compare the 30-day mortality post bloodstream infection of piperacillin/tazobactam and meropenem.
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Timepoint [1]
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30 days
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Secondary outcome [1]
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Time to clinical and microbiologic resolution of infection
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Assessment method [1]
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defined as number of days from randomisation to resolution of fever (temperature \> 38.0o C) and leucocytosis (white blood cell count \>12x109/L) PLUS sterilisation of blood cultures.
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Timepoint [1]
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on or before study day 4
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Secondary outcome [2]
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Clinical and microbiologic success
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Assessment method [2]
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defined as survival PLUS resolution of fever and leucocytosis PLUS sterilisation of blood cultures
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Timepoint [2]
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day 4
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Secondary outcome [3]
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Microbiologic resolution of infection
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Assessment method [3]
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defined as sterility of blood cultures collected on or before day 4
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Timepoint [3]
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day 4
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Secondary outcome [4]
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Microbiologic relapse
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Assessment method [4]
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defined as growth of a meropenem resistant Gram negative bacillus from any clinical specimen collected or a positive stool test (according to local lab diagnostic procedures) for C. difficile, from day 4 of study drug administration to day 30
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Timepoint [4]
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day 30
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Secondary outcome [5]
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Superinfection with a carbapenem or piperacillin-tazobactam resistant organism or Clostridium Difficile
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Assessment method [5]
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To compare the risk of superinfection with a carbapenem resistant organism with each regimen.
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Timepoint [5]
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day 30
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Eligibility
Key inclusion criteria
* Bloodstream infection with E. coli or Klebsiella spp. with proven non-susceptibility to third generation cephalosporins and susceptibility to meropenem and piperacillin-tazobactam from at least one blood culture draw. This will be determined in accordance with laboratory methods and susceptibility breakpoints defined by EUCAST standards (www. eucast.org). Bacterial identification to species level will be performed using standard laboratory methods (e.g. MALDI-TOF) and susceptibility testing (e.g. Vitek2)
* No more than 72 hours has elapsed since the first positive blood culture collection.
* Patient is aged 18 years and over
* The patient or approved proxy is able to provide informed consent.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
* Patient not expected to survive more than 4 days
* Patient allergic to a penicillin or a carbapenem
* Patient with significant polymicrobial bacteraemia (that is, a Gram positive skin contaminant in one set of blood cultures is not regarded as significant polymicrobial bacteraemia).
* Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion).
* Pregnancy or breast-feeding.
* Use of concomitant antimicrobials in the first 4 days after enrolment with known activity against Gram-negative bacilli (except trimethoprim/sulfamethoxazole may be continued as Pneumocystis prophylaxis).
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/02/2014
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
7/08/2017
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Sample size
Target
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Accrual to date
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Final
391
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
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Recruitment hospital [1]
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Shellharbour Hospital (Illawarra Shoalhaven Local Health District) - Shellharbour
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Recruitment hospital [2]
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Westmead Hospital - Westmead
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Wollongong Hospital - Wollongong
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Brisbane Private Hospital - Brisbane
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St. Andrew's War Memorial Hospital - Brisbane
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Recruitment hospital [6]
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Mater Misericordiae Health Services Brisbane Ltd. - Brisbane
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Recruitment hospital [7]
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Royal Brisbane and Women's Hospital - Herston
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Recruitment hospital [8]
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Princess Alexandra Hospital - Woolloongabba
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Recruitment hospital [9]
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Monash Health - Clayton
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Recruitment hospital [10]
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Peter MacCallum Cancer Centre - East Melbourne
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Recruitment hospital [11]
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Barwon Health - Geelong
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Recruitment hospital [12]
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The Alfred Hospital - Melbourne
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Recruitment hospital [13]
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Royal Perth Hospital - Perth
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Recruitment hospital [14]
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Fiona Stanley Hospital - Perth
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Recruitment postcode(s) [1]
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- Shellharbour
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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2500 - Wollongong
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Recruitment postcode(s) [4]
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4000 - Brisbane
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Recruitment postcode(s) [5]
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4001 - Brisbane
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Recruitment postcode(s) [6]
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- Brisbane
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Recruitment postcode(s) [7]
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4029 - Herston
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Recruitment postcode(s) [8]
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4102 - Woolloongabba
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Recruitment postcode(s) [9]
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3168 - Clayton
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Recruitment postcode(s) [10]
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3002 - East Melbourne
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Recruitment postcode(s) [11]
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3220 - Geelong
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Recruitment postcode(s) [12]
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3004 - Melbourne
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Recruitment postcode(s) [13]
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6000 - Perth
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Recruitment postcode(s) [14]
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- Perth
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Recruitment outside Australia
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Canada
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Toronto
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Italy
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Bologna
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Italy
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Milan
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Italy
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Rome
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Italy
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Sanremo
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Italy
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Udine
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Lebanon
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Beirut
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New Zealand
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Papatoetoe
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New Zealand
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Westlake
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Saudi Arabia
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Dammam
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Saudi Arabia
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Riyadh
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Singapore
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Singapore
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South Africa
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Cape Town
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South Africa
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Johannesburg
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Turkey
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Istanbul
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Funding & Sponsors
Primary sponsor type
Other
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Name
The University of Queensland
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Address
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Other collaborator category [1]
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Other
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Name [1]
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International Society of Chemotherapy
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Other collaborator category [2]
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Other
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Name [2]
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Australian Society for Antimicrobials
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Other collaborator category [3]
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Other
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Name [3]
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Queensland Clinical Trials & Biostatistics Centre
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Other
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Name [4]
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Australasian Society for Infectious Diseases
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Ethics approval
Ethics application status
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Summary
Brief summary
No randomized controlled trials (RCTs) have yet been performed comparing different treatment options for AmpC or ESBL-producing Enterobacteriaceae. During the last 10 years we have seen an exponentially increasing rate of carbapenem resistance worldwide, including Australia and New Zealand. The investigators urgently need data from well-designed RCTs to guide clinicians in the treatment of antibiotic resistant Gram-negative infections. The investigators face a situation where a commonly used antibiotic for these infections (meropenem) may be driving carbapenem resistance. For this reason, the investigators are seeking to compare a carbapenem-sparing regimen with a carbapenem for the treatment of these infections. Formal evaluation of safety and efficacy of generic antibiotics in the treatment of infection is of immense clinical and public health importance, and no formal trial has yet been conducted to address these issues. The international collaboration between teams of clinician researchers, some of whom are leaders in their field, makes it highly likely that the outcomes of this trial will have a significant impact on clinical practice. The investigators' hypothesis is that piperacillin/tazobactam (a carbapenem-sparing regimen) is non-inferior to meropenem (a widely used carbapenem) for the definitive treatment of bloodstream infections due to third-generation cephalosporin non-susceptible E. coli or Klebsiella species.
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Trial website
https://clinicaltrials.gov/study/NCT02176122
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Trial related presentations / publications
Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, Alenazi TH, Arabi Y, Falcone M, Bassetti M, Righi E, Rogers BA, Kanj S, Bhally H, Iredell J, Mendelson M, Boyles TH, Looke D, Miyakis S, Walls G, Al Khamis M, Zikri A, Crowe A, Ingram P, Daneman N, Griffin P, Athan E, Lorenc P, Baker P, Roberts L, Beatson SA, Peleg AY, Harris-Brown T, Paterson DL; MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA. 2018 Sep 11;320(10):984-994. doi: 10.1001/jama.2018.12163. Erratum In: JAMA. 2019 Jun 18;321(23):2370. doi: 10.1001/jama.2019.6706. Harris PN, Peleg AY, Iredell J, Ingram PR, Miyakis S, Stewardson AJ, Rogers BA, McBryde ES, Roberts JA, Lipman J, Athan E, Paul SK, Baker P, Harris-Brown T, Paterson DL. Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections due to ceftriaxone non-susceptible Escherichia coli and Klebsiella spp (the MERINO trial): study protocol for a randomised controlled trial. Trials. 2015 Jan 27;16:24. doi: 10.1186/s13063-014-0541-9.
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Public notes
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Contacts
Principal investigator
Name
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David L Paterson, MD, PhD
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Address
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UQCCR, RBWH
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT02176122
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