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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04238390




Registration number
NCT04238390
Ethics application status
Date submitted
16/12/2019
Date registered
23/01/2020

Titles & IDs
Public title
Ceftolozane-tazobactam Versus Meropenem for ESBL and AmpC-producing Enterobacterales Bloodstream Infection
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
Secondary ID [1] 0 0
UQCCR-DP-AS-2019-001
Universal Trial Number (UTN)
Trial acronym
MERINO III
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bacteremia Caused by Gram-Negative Bacteria 0 0
Condition category
Condition code
Blood 0 0 0 0
Other blood disorders
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Studies of infection and infectious agents
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mortality rate at 30 days
Timepoint [1] 0 0
30 days post randomisation
Secondary outcome [1] 0 0
Mortality rate at 14 days
Timepoint [1] 0 0
14 days post randomisation
Secondary outcome [2] 0 0
Clinical and microbiological success
Timepoint [2] 0 0
5 days post randomisation
Secondary outcome [3] 0 0
Functional bacteraemia score (FBS)
Timepoint [3] 0 0
0 and 30 days post randomisation
Secondary outcome [4] 0 0
Microbiological relapse
Timepoint [4] 0 0
30 days post randomisation
Secondary outcome [5] 0 0
Rates of new bloodstream infection
Timepoint [5] 0 0
30 days post randomisation
Secondary outcome [6] 0 0
Length of in-patient hospital and ICU stay
Timepoint [6] 0 0
30 days post randomisation
Secondary outcome [7] 0 0
Serious adverse events
Timepoint [7] 0 0
Day 1 to last dose plus 24 hours of treatment:
Secondary outcome [8] 0 0
Clostridioides difficile infection
Timepoint [8] 0 0
30 days post randomisation
Secondary outcome [9] 0 0
Colonisation and/or infection with multi-resistant bacterial organisms
Timepoint [9] 0 0
30 days post randomisation
Secondary outcome [10] 0 0
Desirability of Outcome Ranking (DOOR) with partial credit
Timepoint [10] 0 0
30 days post randomisation

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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/01/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Hospital - Newcastle
Recruitment hospital [2] 0 0
Royal Prince Alfred - Sydney
Recruitment hospital [3] 0 0
Westmead Hospital - Sydney
Recruitment hospital [4] 0 0
Woolongong Hospital - Wollongong
Recruitment hospital [5] 0 0
Royal Brisbane and Women's Hospital - Brisbane
Recruitment hospital [6] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [7] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [8] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [9] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [10] 0 0
Dandenong Hospital - Melbourne
Recruitment hospital [11] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [12] 0 0
Sir Charles Gairdner - Perth
Recruitment hospital [13] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
2305 - Newcastle
Recruitment postcode(s) [2] 0 0
2050 - Sydney
Recruitment postcode(s) [3] 0 0
2145 - Sydney
Recruitment postcode(s) [4] 0 0
2500 - Wollongong
Recruitment postcode(s) [5] 0 0
4029 - Brisbane
Recruitment postcode(s) [6] 0 0
4102 - Brisbane
Recruitment postcode(s) [7] 0 0
3000 - Melbourne
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3168 - Melbourne
Recruitment postcode(s) [10] 0 0
3175 - Melbourne
Recruitment postcode(s) [11] 0 0
6000 - Perth
Recruitment postcode(s) [12] 0 0
6009 - Perth
Recruitment postcode(s) [13] 0 0
6150 - Perth
Recruitment outside Australia
Country [1] 0 0
Italy
State/province [1] 0 0
Bologna
Country [2] 0 0
Italy
State/province [2] 0 0
Milan
Country [3] 0 0
Italy
State/province [3] 0 0
Pisa
Country [4] 0 0
Italy
State/province [4] 0 0
Roma
Country [5] 0 0
Italy
State/province [5] 0 0
Sanremo
Country [6] 0 0
Saudi Arabia
State/province [6] 0 0
Dammam
Country [7] 0 0
Saudi Arabia
State/province [7] 0 0
Jeddah
Country [8] 0 0
Saudi Arabia
State/province [8] 0 0
Riyadh
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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/NCT04238390