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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04238390
Registration number
NCT04238390
Ethics application status
Date submitted
16/12/2019
Date registered
23/01/2020
Date last updated
19/05/2022
Titles & IDs
Public title
Ceftolozane-tazobactam Versus Meropenem for ESBL and AmpC-producing Enterobacterales Bloodstream Infection
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Scientific title
A Multicentre, Parallel Group Open-label Randomised Controlled Non-Inferiority Phase 3 Trial, of Ceftolozane-tazobactam Versus Meropenem for Definitive Treatment of Bloodstream Infection Due to Extended-Spectrum Beta-Lactamase (ESBL) and AmpC-producing Enterobacterales
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Secondary ID [1]
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UQCCR-DP-AS-2019-001
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Universal Trial Number (UTN)
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Trial acronym
MERINO III
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Bacteremia Caused by Gram-Negative Bacteria
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Condition category
Condition code
Blood
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Other blood disorders
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Infection
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Other infectious diseases
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Infection
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Studies of infection and infectious agents
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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 - Ceftolozane-Tazobactam
Treatment: Drugs - Meropenem
Experimental: Ceftolozane-tazobactam - Participants will receive ceftolozane-tazobactam 3 grams (comprising ceftolozane 2 grams and tazobactam 1 gram) administered, every 8 hours, three times a day, intravenously over 60 mins
Active Comparator: Meropenem - Participants will receive meropenem 1 gram, every 8 hours, three times a day, intravenously over 30 mins.
Treatment: Drugs: Ceftolozane-Tazobactam
Ceftolozane-tazobactam 3 grams (comprising ceftolozane 2 grams and tazobactam 1 gram) administered, every 8 hours, three times a day, intravenously over 60 mins. Dose adjusted for renal function.
Treatment: Drugs: Meropenem
Meropenem 1 gram, every 8 hours, three times a day, intravenously over 30 mins. Dose adjusted for renal function.
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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 rate at 30 days
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Assessment method [1]
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To compare the 30-day mortality from day of randomisation of each regimen
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Timepoint [1]
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30 days post randomisation
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Secondary outcome [1]
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Mortality rate at 14 days
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Assessment method [1]
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To compare the 14-day mortality from day of randomisation of each regimen
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Timepoint [1]
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14 days post randomisation
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Secondary outcome [2]
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Clinical and microbiological success
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Assessment method [2]
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Defined as survival PLUS resolution of fever (temperature <38 degrees Celsius) PLUS improved SOFA score (as compared to baseline) PLUS sterilisation of blood cultures at Day 5
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Timepoint [2]
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5 days post randomisation
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Secondary outcome [3]
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Functional bacteraemia score (FBS)
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Assessment method [3]
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To compare the functional bacteraemia score of patients treated with each regimen at baseline and Day 30 (scored 0-7, higher scores equal better outcomes)
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Timepoint [3]
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0 and 30 days post randomisation
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Secondary outcome [4]
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Microbiological relapse
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Assessment method [4]
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To compare the rates of relapse of bloodstream infection (microbiological failure) with each regimen at Day 30
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Timepoint [4]
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30 days post randomisation
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Secondary outcome [5]
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Rates of new bloodstream infection
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Assessment method [5]
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To compare the rates of new bloodstream infection (growth of a new organism from blood cultures - not a contaminant as determined by treating clinician) with each regimen
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Timepoint [5]
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30 days post randomisation
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Secondary outcome [6]
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Length of in-patient hospital and ICU stay
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Assessment method [6]
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To compare lengths of in-patient hospital and ICU stay with each regimen (not including in-patient rehabilitation, long term acute care or hospital in the home)
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Timepoint [6]
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30 days post randomisation
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Secondary outcome [7]
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Serious adverse events
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Assessment method [7]
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To compare the number of treatment emergent serious adverse events with each regimen
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Timepoint [7]
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Day 1 to last dose plus 24 hours of treatment:
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Secondary outcome [8]
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Clostridioides difficile infection
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Assessment method [8]
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To compare rates of Clostridioides difficile infection with each regimen
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Timepoint [8]
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30 days post randomisation
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Secondary outcome [9]
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Colonisation and/or infection with multi-resistant bacterial organisms
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Assessment method [9]
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To compare rates of colonisation and/or infection with multi-resistant bacterial organisms (MROs) including those newly acquired
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Timepoint [9]
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30 days post randomisation
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Secondary outcome [10]
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Desirability of Outcome Ranking (DOOR) with partial credit
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Assessment method [10]
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To compare the Desirability of Outcome Ranking (DOOR) with partial credit with each regimen (scored 0-100, higher scores equal better outcomes)
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Timepoint [10]
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30 days post randomisation
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Eligibility
Key inclusion criteria
- Bloodstream infection defined as presence in at least one peripheral blood culture
draw demonstrating Enterobacterales with proven non-susceptibility to third generation
cephalosporins or cephalosporin susceptible species known to harbour chromosomal
AmpC-beta-lactamases (Enterobacter spp., Klebsiella aerogenes, Citrobacter freundii,
Morganella morganii, Providencia spp. or Serratia marcescens) during hospitalisation
- Patient is aged 18 years and over (21 and over in Singapore)
- The patient or approved proxy is able to provide informed consent
- =72 hours has elapsed since the first positive qualifying (index) blood culture
collection
- Expected to receive IV therapy for =5 days
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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
- Known hypersensitivity to a cephalosporin or a carbapenem, or anaphylaxis to
beta-lactam antibiotics
- Participant with significant polymicrobial bloodstream infection (i.e. not a
contaminant)
- Treatment is not with the intent to cure the infection (i.e. palliative intent) or the
expected survival is =4 days
- Participant is pregnant or breast-feeding (tested for in women of child-bearing age
only)
- Use of concomitant antimicrobials with known activity against Gram-negative bacilli
(except trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis and when adding
metronidazole for suspected IAI) in the first 5 days post-randomisation
- Participant with CrCl <15 mL/minute or on renal replacement therapy (in addition,
participants will be withdrawn from the study if CrCl reaches this level)
- Previously randomised in the MERINO-3 trial or concurrently enrolled in another
therapeutic antibiotic clinical trial
- Blood culture isolate with in-vitro resistance to either meropenem or
ceftolozane-tazobactam (known either at time of enrolment or during the course of
study treatment, in which case the participant will be withdrawn)
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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 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Withdrawn
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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
1/01/2022
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Actual
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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
1/12/2024
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Actual
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Sample size
Target
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Accrual to date
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Final
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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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John Hunter Hospital - Newcastle
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Recruitment hospital [2]
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Royal Prince Alfred - Sydney
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Recruitment hospital [3]
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Westmead Hospital - Sydney
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Recruitment hospital [4]
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Woolongong Hospital - Wollongong
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Recruitment hospital [5]
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Royal Brisbane and Women's Hospital - Brisbane
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Recruitment hospital [6]
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Princess Alexandra Hospital - Brisbane
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Recruitment hospital [7]
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Peter MacCallum Cancer Centre - Melbourne
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Recruitment hospital [8]
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Alfred Hospital - Melbourne
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Recruitment hospital [9]
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Monash Medical Centre - Melbourne
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Recruitment hospital [10]
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Dandenong Hospital - Melbourne
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Recruitment hospital [11]
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Royal Perth Hospital - Perth
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Recruitment hospital [12]
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Sir Charles Gairdner - Perth
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Recruitment hospital [13]
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Fiona Stanley Hospital - Perth
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Recruitment postcode(s) [1]
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2305 - Newcastle
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Recruitment postcode(s) [2]
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2050 - Sydney
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Recruitment postcode(s) [3]
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2145 - Sydney
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Recruitment postcode(s) [4]
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2500 - Wollongong
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Recruitment postcode(s) [5]
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4029 - Brisbane
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Recruitment postcode(s) [6]
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4102 - Brisbane
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Recruitment postcode(s) [7]
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3000 - Melbourne
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Recruitment postcode(s) [8]
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3004 - Melbourne
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Recruitment postcode(s) [9]
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3168 - Melbourne
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Recruitment postcode(s) [10]
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3175 - Melbourne
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Recruitment postcode(s) [11]
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6000 - Perth
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Recruitment postcode(s) [12]
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6009 - Perth
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Recruitment postcode(s) [13]
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6150 - Perth
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Recruitment outside Australia
Country [1]
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Italy
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State/province [1]
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Bologna
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Country [2]
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Italy
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State/province [2]
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Milan
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Country [3]
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Italy
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State/province [3]
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Pisa
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Country [4]
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Italy
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State/province [4]
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Roma
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Country [5]
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Italy
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State/province [5]
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Sanremo
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Country [6]
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Saudi Arabia
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State/province [6]
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Dammam
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Country [7]
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Saudi Arabia
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State/province [7]
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Jeddah
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Country [8]
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Saudi Arabia
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State/province [8]
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Riyadh
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Country [9]
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Singapore
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State/province [9]
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Singapore
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Country [10]
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Spain
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State/province [10]
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Barcelona
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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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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Merck Sharp & Dohme LLC
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Address [1]
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Country [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study is to determine whether ceftolozane-tazobactam is as effective as
meropenem with respect to 30 day mortality in the treatment of bloodstream infection due to
third-generation cephalosporin non-susceptible Enterobacterales or a known chromosomal
AmpC-producing Enterobacterales (Enterobacter spp., Citrobacter freundii, Morganella
morganii, Providencia spp. or Serratia marcescens).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04238390
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04238390
Download to PDF