Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
- Conditions
- Gram-Negative Bacterial Infections
- Interventions
- Registration Number
- NCT01732250
- Lead Sponsor
- Mical Paul
- Brief Summary
The purpose of this study is to determine whether the addition of meropenem to colistin is better than colistin alone in the treatment of clinically significant infections caused by multi-drug resistant bacteria
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 406
- Adult inpatients
- Clinically significant, microbiological-documented infection caused by carbapenem-resistant and colistin-susceptible Gram-negative bacteria and identified according to CDC criteria- blood stream infections, hospital acquired pneumonia, ventilator associated pneumonia, and urinary tract infections
- Patient recruitment will occur only after microbiological documentation and susceptibility testing. Patients will be included within 96 hours of the time the index culture was taken (typically within 48 hours of isolate identification), regardless of the antibiotic treatment administered during this time period.
- Previous inclusion in the trial. Patients will be included in the RCT only once for the first identified episode of infection
- Pregnant women
- Epilepsy or prior seizures
- Known allergy to colistin or a carbapenem
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Colistin and Meropenem Colistin IV meropenem, 2 gram q8h, adjusted for renal function IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function Colistin and Meropenem Meropenem IV meropenem, 2 gram q8h, adjusted for renal function IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function Colistin Colistin IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function
- Primary Outcome Measures
Name Time Method Clinical success 14 days defined as a composite of all of the following, all measured at 14 days:
* Patient alive
* Systolic blood pressure \>90 mmHg without need for vasopressor support
* Stable or improved SOFA score, define as:
* for baseline SOFA ≥ 3: a decrease of at least 30%;
* for baseline SOFA \<3: stable or decreased SOFA score
* For patients with HAP/ VAP, PaO2/FiO2 ratio stable or improved
* For patients with bacteremia, no growth of the initial isolate in blood cultures taken on day 14 if patient still febrile
- Secondary Outcome Measures
Name Time Method Time to defervescence 28 days defined as time to reach a temperature of \<38°C with no recurrence for 3 days
CDAD 28 days Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test
Time to weaning 28 days Time to weaning from mechanical ventilation in VAP for patients weaned alive
Microbiological failure 28 days Microbiological failure, defined as isolation of the initial isolate (phenotypically identical) in a clinical sample (blood or other) 7 days or more after start of treatment or its identification in respiratory samples.
* For all patients with VAP/ HAP sputum or tracheal aspirates will be obtained on day 7, regardless of clinical response
* For all patients with UTI, a repeat urine culture will be obtained on day 7, regardless of clinical response
* For patients with bacteremia, blood cultures will be repeated on day 7 and 14, only if the patient is febrile at that timeNew resistant infection 28 days Colonization or infection by newly-acquired (other species than the initial infection) carbapenem-resistant or colistin-resistant Gram-negative bacteria. Colonization will be assessed by rectal surveillance
Secondary outcomes and adverse events 14 and 28 days 14 and 28-day all-cause mortality.
If patients are discharged or death occurs before end of follow-up (day 28), we will end data collection at that date. We will attempt to determine survival status at day 28 for all patients (central registry in Israel; re-admissions, rehabilitation centers, hospital transfers in Greece and Italy).Clinical success with modification 14 days Clinical success, but with modification to the antibiotic treatment not permitted by protocol
Time to hospital discharge 28 days Time to hospital discharge for patient discharged alive
Superinfections 28 days Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days
Trial Locations
- Locations (7)
Tel-Aviv Sourasky Medical Center
🇮🇱Tel-Aviv, Israel
Rambam Health Care Center
🇮🇱Haifa, Israel
Laikon Hosptial
🇬🇷Athens, Greece
Rabin Medical Center
🇮🇱Petach-Tikvah, Israel
Atikkon Hospital
🇬🇷Athens, Greece
Agostino Gemelli Hospital
🇮🇹Rome, Italy
Monaldi Hospital, University of Naples S.U.N.
🇮🇹Naples, Italy