Ceftolozane-tazobactam Versus Meropenem for ESBL and AmpC-producing Enterobacterales Bloodstream Infection (MERINO III)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04238390|
Recruitment Status : Not yet recruiting
First Posted : January 23, 2020
Last Update Posted : January 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Bacteremia Caused by Gram-Negative Bacteria||Drug: Ceftolozane-Tazobactam Drug: Meropenem||Phase 3|
Enterobacterales are common causes of bacteraemia, and may produce extended-spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases. ESBL or AmpC producers are typically resistant to third generation cephalosporins such as ceftriaxone, but susceptible to carbapenems. In no study has the outcome of treatment for serious infections for ESBL producers been significantly surpassed by carbapenems. Despite the potential advantages of carbapenems for treatment of ceftriaxone non-susceptible organisms, widespread use of carbapenems may cause selection pressure leading to carbapenem-resistant organisms. This is a significant issue since carbapenem-resistant organisms are treated with last-line antibiotics such as colistin.
Ceftolozane-tazobactam is a combination of a new beta-lactam antibiotic with an existing beta-lactamase inhibitor, tazobactam, and is active against ESBL and most AmpC producing organisms. In a large sample of ESBL- and AmpC-producing Enterobacterales isolates from urinary tract and intra-abdominal specimens, ceftolozane-tazobactam was susceptible in over 80%. It has been FDA approved for complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI), and more recently for hospital-acquired and ventilator-associated pneumonia (HAP/VAP). In addition, a pooled analysis of phase 3 clinical trials has shown favourable clinical cure rates with ceftolozane-tazobactam for cUTI and cIAI caused by ESBL-producing Enterobacterales. Given the issues of carbapenem resistant organisms, there is a need for establishing the efficacy of an alternative to carbapenems for serious infections.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||630 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official 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|
|Estimated Study Start Date :||June 1, 2020|
|Estimated Primary Completion Date :||June 1, 2024|
|Estimated Study Completion Date :||December 1, 2024|
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
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.
Active Comparator: Meropenem
Participants will receive meropenem 1 gram, every 8 hours, three times a day, intravenously over 30 mins.
Meropenem 1 gram, every 8 hours, three times a day, intravenously over 30 mins. Dose adjusted for renal function.
- Mortality rate at 30 days [ Time Frame: 30 days post randomisation ]To compare the 30-day mortality from day of randomisation of each regimen
- Mortality rate at 14 days [ Time Frame: 14 days post randomisation ]To compare the 14-day mortality from day of randomisation of each regimen
- Clinical and microbiological success [ Time Frame: 5 days post randomisation ]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
- Functional bacteraemia score (FBS) [ Time Frame: 0 and 30 days post randomisation ]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)
- Microbiological relapse [ Time Frame: 30 days post randomisation ]To compare the rates of relapse of bloodstream infection (microbiological failure) with each regimen at Day 30
- Rates of new bloodstream infection [ Time Frame: 30 days post randomisation ]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
- Length of in-patient hospital and ICU stay [ Time Frame: 30 days post randomisation ]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)
- Serious adverse events [ Time Frame: Day 1 to last dose plus 24 hours of treatment: ]To compare the number of treatment emergent serious adverse events with each regimen
- Clostridioides difficile infection [ Time Frame: 30 days post randomisation ]To compare rates of Clostridioides difficile infection with each regimen
- Colonisation and/or infection with multi-resistant bacterial organisms [ Time Frame: 30 days post randomisation ]To compare rates of colonisation and/or infection with multi-resistant bacterial organisms (MROs) including those newly acquired
- Desirability of Outcome Ranking (DOOR) with partial credit [ Time Frame: 30 days post randomisation ]To compare the Desirability of Outcome Ranking (DOOR) with partial credit with each regimen (scored 0-100, higher scores equal better outcomes)
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): NCT04238390
|Contact: Adam G Stewart, MBBSemail@example.com|
|Contact: Roberta Littleford, PhDfirstname.lastname@example.org|