Trial of Meropenem Versus Piperacillin-Tazobactam on Mortality and Clinial Response (MERINO II)
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|ClinicalTrials.gov Identifier: NCT02437045|
Recruitment Status : Recruiting
First Posted : May 7, 2015
Last Update Posted : May 2, 2018
|Condition or disease||Intervention/treatment||Phase|
|Bloodstream Infections||Drug: Meropenem Drug: Piperacillin-tazobactam combination product||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Study Start Date :||April 2015|
|Estimated Primary Completion Date :||September 2020|
|Estimated Study Completion Date :||September 2020|
Active Comparator: Meropenem
Meropenem 1g every 8 hrs IV to day 4
Meropenem is a carbapenem anti-bacterial used for the treatment of serious infections in patients.
Experimental: Piperacillin-tazobactam combination product
Piperacillin tazobactam 4.5g every 6 hrs IV to day 4
Drug: Piperacillin-tazobactam combination product
Piperacillin-tazobactam is used for the treatment of patients with systemic and/or local bacterial infections.
- Clinical and microbiological outcomes post bloodstream infection of patients treated with piperacillin/tazobactam and meropenem. [ Time Frame: Composite end point; up to day 30. ]
Composite end-point of:
Death: up to 30 days post randomisation. Clinical failure - defined as ongoing fever (Tmax >=38.0oC) OR leucocytosis (white blood cell count >12x109/L) - assessed on day 5 post randomisation.
Microbiological failure - defined as positive blood culture or any sterile site specimen with same species as initial (index) blood culture on day 3-5.
Microbiological relapse - defined as growth from any sterile site of the same organism as in the original blood culture after day 5 but before day 30; If any of the above criteria are fulfilled post randomisation, the composite end-point has occurred. A composite end-point has been used as overall mortality is expected to be low in this subset of patients screened for 'low-risk' infections, and so is unlikely to be a useful primary outcome measure in isolation.
- Time to clinical resolution of infection. [ Time Frame: 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. ]Time to clinical resolution of infection - defined as number of days from randomisation to resolution of fever (temperature >= 38.0 C)
- Clinical and microbiological success day 5. [ Time Frame: Day five. ]Clinical and microbiological success day 5 - defined as composite result of survival PLUS resolution of fever and leucocytosis (white blood cell count >12x109/L) PLUS sterilisation of blood cultures by day 5 post randomisation .
- Length of hospital and/or ICU stay post randomisation. [ Time Frame: Participants will be followed for the duration of their hospitalisation and/or up to the thirty day study time period. ]Length of hospital and/or ICU stay post randomisation.
- Requirement for ICU admission: if not in ICU at the time of enrolment, during days 1 to 5 post-randomisation. [ Time Frame: Days 1-5. ]Requirement for ICU admission: if not in ICU at the time of enrolment, during days 1 to 5 post-randomisation.
- Infection with a piperacillin-tazobactam / carbapenem resistant organism or Clostridium difficile. [ Time Frame: Days 5-30. ]Infection with a piperacillin-tazobactam / carbapenem resistant organism or Clostridium difficile - defined as composite result of growth of a meropenem or piperacillin-tazobactam resistant Gram-negative organism from any clinical (non-screening) specimen collected from day 5 post randomisation to day 30. A positive stool test for Clostridium difficile (by toxin EIA and/or PCR, depending on the laboratory protocol of the study site) will also be recorded. This endpoint is important since one of the purposes of establishing an alternative to carbapenem therapy is to reduce infections with multi-drug resistant organisms and assess the comparative risk of C. difficile.
- Microbiological failure with AmpC-mediated resistance. [ Time Frame: After day 5 before day 30. ]Microbiological failure with AmpC-mediated resistance -- defined as growth of the same Enterobacter, Serratia, Providencia spp., Morganella morganii or Citrobacter freundii as in the original blood culture from any blood culture or other clinical sample taken after day 5 but before 30 days - with emergent resistance likely due to AmpC de-repression (i.e. resistance to third generation cephalosporins, and /or piperacillin-tazobactam), and re-infection by new strain excluded by molecular typing.
- Colonisation with any multi-drug resistant organism. [ Time Frame: Days 1-30. ]Colonisation with any multi-drug resistant organism - defined as the isolation from any screening site (nose/groin/axilla/rectal swabs) of multi-drug resistant bacteria (i.e. MRSA, VRE, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas or Acinetobacter) at any time from study enrolment to 30 days post initial blood culture collection. This will include any swabs or other specimens collected as part of routine clinical care at all study sites; at the RBWH site this will also include screening swabs taken at specific time-points for enhanced surveillance.
- Requirement for escalation of antibiotic therapy. [ Time Frame: Days 1-5. ]Requirement for escalation of antibiotic therapy (i.e. piperacillin-tazobactam to meropenem) or addition of second Gram-negative agent days 1 to 5.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02437045
|Contact: David Paterson, Professoremail@example.com|
|Contact: Patrick Harris, Drfirstname.lastname@example.org|
|Australia, New South Wales|
|John Hunter Hospital||Recruiting|
|New Lambton, New South Wales, Australia, 2305|
|Contact: Joshua Davis, Doctor Joshua.Davis@menzies.edu.au|
|Wollongong, New South Wales, Australia|
|Contact: Spiros Miyakis, Doctor email@example.com|
|Princess Alexandra Hospital||Recruiting|
|Brisbane, Queensland, Australia, 4101|
|Contact: Naomi Runnegar, Doctor Naomi.Runnegar@health.qld.gov.au|
|Royal Brisbane Hospital||Recruiting|
|Brisbane, Queensland, Australia, 4170|
|Contact: David Paterson, Professor firstname.lastname@example.org|
|National University Hospital Singapore||Not yet recruiting|
|Contact: Sophia Archula, Doctor email@example.com|
|Tan Tock Seng Hospital||Not yet recruiting|
|Contact: Barnaby Young, Doctor firstname.lastname@example.org|
|Principal Investigator:||David Paterson, Professor||The University of Queensland Centre for Clinical Research|