Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
Study Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Colistin and 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 |
Drug: Colistin
IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function, for 10 days.
Other Names:
Drug: Meropenem
IV meropenem, 2 gram q8h, adjusted for renal function, for up to 10 days.
Other Names:
|
| Active Comparator: Colistin IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function |
Drug: Colistin
IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function, for 10 days.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 defervescence [28 days]
defined as time to reach a temperature of <38°C with no recurrence for 3 days
- Time to weaning [28 days]
Time to weaning from mechanical ventilation in VAP for patients weaned alive
- Time to hospital discharge [28 days]
Time to hospital discharge for patient discharged 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 time
- Superinfections [28 days]
Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days
- New 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
- CDAD [28 days]
Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Atikkon Hospital | Athens | Greece | ||
| 2 | Laikon Hosptial | Athens | Greece | ||
| 3 | Rambam Health Care Center | Haifa | Israel | ||
| 4 | Rabin Medical Center | Petach-Tikvah | Israel | ||
| 5 | Tel-Aviv Sourasky Medical Center | Tel-Aviv | Israel | ||
| 6 | Monaldi Hospital, University of Naples S.U.N. | Naples | Italy | ||
| 7 | Agostino Gemelli Hospital | Rome | Italy |
Sponsors and Collaborators
- Mical Paul
- European Commission
Investigators
- Study Chair: Johan Mouton, MD PhD, Radboud University Medical Center
- Principal Investigator: Mical Paul, MD, Rambam Health Care Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 0276-12-RMC