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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02437045




Registration number
NCT02437045
Ethics application status
Date submitted
20/04/2015
Date registered
7/05/2015
Date last updated
10/05/2023

Titles & IDs
Public title
Trial of Meropenem Versus Piperacillin-Tazobactam on Mortality and Clinial Response
Scientific title
Pilot RCT of Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC Beta-lactamase Producing Enterobacter Spp., Citrobacter Freundii, Morganella Morganii, Providencia Spp. or Serratia Marcescens. in Low-risk Patients
Secondary ID [1] 0 0
HREC/14/QRBW/350
Universal Trial Number (UTN)
Trial acronym
MERINO II
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 every 8 hrs IV to day 4

Experimental: Piperacillin-tazobactam combination product - Piperacillin tazobactam 4.5g every 6 hrs IV to 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
Clinical and microbiological outcomes post bloodstream infection of patients treated with piperacillin/tazobactam and meropenem.
Timepoint [1] 0 0
Composite end point; up to day 30.
Secondary outcome [1] 0 0
Time to clinical resolution of infection.
Timepoint [1] 0 0
Resolution of infection will be monitored from day of randomisation up to study day five or when the patient exhibits a temperature below 38 degrees celcius.
Secondary outcome [2] 0 0
Clinical and microbiological success day 5.
Timepoint [2] 0 0
Day five.
Secondary outcome [3] 0 0
Length of hospital and/or ICU stay post randomisation.
Timepoint [3] 0 0
Participants will be followed for the duration of their hospitalisation and/or up to the thirty day study time period.
Secondary outcome [4] 0 0
Requirement for ICU admission: if not in ICU at the time of enrolment, during days 1 to 5 post-randomisation.
Timepoint [4] 0 0
Days 1-5.
Secondary outcome [5] 0 0
Infection with a piperacillin-tazobactam / carbapenem resistant organism or Clostridium difficile.
Timepoint [5] 0 0
Days 5-30.
Secondary outcome [6] 0 0
Microbiological failure with AmpC-mediated resistance.
Timepoint [6] 0 0
After day 5 before day 30.
Secondary outcome [7] 0 0
Colonisation with any multi-drug resistant organism.
Timepoint [7] 0 0
Days 1-30.
Secondary outcome [8] 0 0
Requirement for escalation of antibiotic therapy.
Timepoint [8] 0 0
Days 1-5.

Eligibility
Key inclusion criteria
* Bloodstream infection with Enterobacter spp., Serratia marcescens, Providencia spp., Morganella morganii or Citrobacter freundii (i.e. likely AmpC-producer), and susceptibility to 3rd generation cephalosporins (i.e. ceftriaxone, cefotaxime or ceftazidime), 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 protocols used in the recruiting site laboratories..
* No more than 72 hours has elapsed since the first positive blood culture collection.
* Patient is aged 18 years and over (>=21y in Singapore).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient not expected to survive more than 4 days
2. Patient allergic to a penicillin or a carbapenem
3. 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).
4. Treatment is not with the intent to cure the infection (that is, palliative care is an exclusion).
5. Pregnancy or breast-feeding.
6. Use of concomitant antimicrobials in the first 4 days after enrolment with known activity against Gram-negative bacilli (except trimethoprim/sulphamethoxazole may be continued as Pneumocystis prophylaxis).
7. Severe acute illness as defined by Pitt bacteraemia score of >4
8. Likely source to be from (proven or suspected at the time of randomisation) the central nervous system, e.g. brain abscess, post-surgical meningitis, shunt infection (due to concerns over CNS penetration of piperacillin/tazobactam)

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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/12/2020
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [2] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Brisbane Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
2305 - New Lambton
Recruitment postcode(s) [2] 0 0
- Wollongong
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
4170 - Brisbane
Recruitment outside Australia
Country [1] 0 0
Singapore
State/province [1] 0 0
Singapore

Funding & Sponsors
Primary sponsor type
Other
Name
The University of Queensland
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Infections of the blood are extremely serious and require intravenous antibiotic treatment. When the infection results from antibiotic resistant bacteria, the choice of antibiotic is an extremely important decision. Some types of bacteria produce enzymes that may inactivate essential antibiotics, related to penicillin, called 'beta-lactams'. Furthermore high level production of these enzymes can occur during therapy and lead to clinical failure, even when an antibiotic appears effective by laboratory testing. However, this risk of this occurring in clinical practice has only been well described in a limited range of antibiotic classes in a type of bacteria called Enterobacter. There is currently uncertainty as to whether a commonly used, and highly effective antibiotic, called piperacillin-tazobactam is subject to the same risk of resistance developing while on treatment. Infections caused by Enterobacter (and other bacteria with similar resistance mechanisms) are often treated with an alternative drug called meropenem (a carbapenem antibiotic), which is effective but has an extremely broad-spectrum of activity. Excessive use of carbapenems is driving further resistance to this antibiotic class - which represent our 'lastline' of antibiotic defence. As such, we need studies to help us see whether alternatives to meropenem are an effective and safe choice. No study has ever directly tested whether these two antibiotics have the same effectiveness for this type of infection. The purpose of this study is to randomly assign patients with blood infection caused by Enterobacter or related bacteria to either meropenem or piperacillin/tazobactam in order to test whether these antibiotics have similar effectiveness.
Trial website
https://clinicaltrials.gov/study/NCT02437045
Trial related presentations / publications
Stewart AG, Paterson DL, Young B, Lye DC, Davis JS, Schneider K, Yilmaz M, Dinleyici R, Runnegar N, Henderson A, Archuleta S, Kalimuddin S, Forde BM, Chatfield MD, Bauer MJ, Lipman J, Harris-Brown T, Harris PNA; MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC beta-Lactamase-Producing Enterobacter spp, Citrobacter freundii, Morganella morganii, Providencia spp, or Serratia marcescens: A Pilot Multicenter Randomized Controlled Trial (MERINO-2). Open Forum Infect Dis. 2021 Aug 2;8(8):ofab387. doi: 10.1093/ofid/ofab387. eCollection 2021 Aug.
Public notes

Contacts
Principal investigator
Name 0 0
David Paterson, Professor
Address 0 0
The University of Queensland Centre for Clinical Research
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/study/NCT02437045