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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/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.
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.
Secondary ID [1] 0 0
ACTRN12613000532707
Universal Trial Number (UTN)
Trial acronym
MERINO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Bloodstream Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
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 - 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mortality at 30 days
Timepoint [1] 0 0
30 days
Secondary outcome [1] 0 0
Time to clinical and microbiologic resolution of infection
Timepoint [1] 0 0
on or before study day 4
Secondary outcome [2] 0 0
Clinical and microbiologic success
Timepoint [2] 0 0
day 4
Secondary outcome [3] 0 0
Microbiologic resolution of infection
Timepoint [3] 0 0
day 4
Secondary outcome [4] 0 0
Microbiologic relapse
Timepoint [4] 0 0
day 30
Secondary outcome [5] 0 0
Superinfection with a carbapenem or piperacillin-tazobactam resistant organism or Clostridium Difficile
Timepoint [5] 0 0
day 30

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

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 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
7/08/2017
Sample size
Target
Accrual to date
Final
391
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Shellharbour Hospital (Illawarra Shoalhaven Local Health District) - Shellharbour
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [4] 0 0
Brisbane Private Hospital - Brisbane
Recruitment hospital [5] 0 0
St. Andrew's War Memorial Hospital - Brisbane
Recruitment hospital [6] 0 0
Mater Misericordiae Health Services Brisbane Ltd. - Brisbane
Recruitment hospital [7] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [8] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [9] 0 0
Monash Health - Clayton
Recruitment hospital [10] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment hospital [11] 0 0
Barwon Health - Geelong
Recruitment hospital [12] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [13] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [14] 0 0
Fiona Stanley Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Shellharbour
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
2500 - Wollongong
Recruitment postcode(s) [4] 0 0
4000 - Brisbane
Recruitment postcode(s) [5] 0 0
4001 - Brisbane
Recruitment postcode(s) [6] 0 0
- Brisbane
Recruitment postcode(s) [7] 0 0
4029 - Herston
Recruitment postcode(s) [8] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3002 - East Melbourne
Recruitment postcode(s) [11] 0 0
3220 - Geelong
Recruitment postcode(s) [12] 0 0
3004 - Melbourne
Recruitment postcode(s) [13] 0 0
6000 - Perth
Recruitment postcode(s) [14] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Toronto
Country [2] 0 0
Italy
State/province [2] 0 0
Bologna
Country [3] 0 0
Italy
State/province [3] 0 0
Milan
Country [4] 0 0
Italy
State/province [4] 0 0
Rome
Country [5] 0 0
Italy
State/province [5] 0 0
Sanremo
Country [6] 0 0
Italy
State/province [6] 0 0
Udine
Country [7] 0 0
Lebanon
State/province [7] 0 0
Beirut
Country [8] 0 0
New Zealand
State/province [8] 0 0
Papatoetoe
Country [9] 0 0
New Zealand
State/province [9] 0 0
Westlake
Country [10] 0 0
Saudi Arabia
State/province [10] 0 0
Dammam
Country [11] 0 0
Saudi Arabia
State/province [11] 0 0
Riyadh
Country [12] 0 0
Singapore
State/province [12] 0 0
Singapore
Country [13] 0 0
South Africa
State/province [13] 0 0
Cape Town
Country [14] 0 0
South Africa
State/province [14] 0 0
Johannesburg
Country [15] 0 0
Turkey
State/province [15] 0 0
Istanbul

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
International Society of Chemotherapy
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australian Society for Antimicrobials
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Queensland Clinical Trials & Biostatistics Centre
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
Australasian Society for Infectious Diseases
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02176122
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David L Paterson, MD, PhD
Address 0 0
UQCCR, RBWH
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02176122