Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
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ClinicalTrials.gov Identifier: NCT01732250 |
Recruitment Status :
Completed
First Posted : November 22, 2012
Last Update Posted : April 12, 2017
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Condition or disease | Intervention/treatment | Phase |
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Gram-Negative Bacterial Infections | Drug: Colistin Drug: Meropenem | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 406 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem |
Actual Study Start Date : | March 2013 |
Actual Primary Completion Date : | January 31, 2017 |
Actual Study Completion Date : | February 28, 2017 |

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
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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 Name: Meronem |
Active Comparator: Colistin
IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function
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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:
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- Clinical success [ Time Frame: 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
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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 outcomes and adverse events [ Time Frame: 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 [ Time Frame: 14 days ]Clinical success, but with modification to the antibiotic treatment not permitted by protocol
- Time to defervescence [ Time Frame: 28 days ]defined as time to reach a temperature of <38°C with no recurrence for 3 days
- Time to weaning [ Time Frame: 28 days ]Time to weaning from mechanical ventilation in VAP for patients weaned alive
- Time to hospital discharge [ Time Frame: 28 days ]Time to hospital discharge for patient discharged alive
- Microbiological failure [ Time Frame: 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 [ Time Frame: 28 days ]Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days
- New resistant infection [ Time Frame: 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 [ Time Frame: 28 days ]Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

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): NCT01732250
Greece | |
Atikkon Hospital | |
Athens, Greece | |
Laikon Hosptial | |
Athens, Greece | |
Israel | |
Rambam Health Care Center | |
Haifa, Israel | |
Rabin Medical Center | |
Petach-Tikvah, Israel | |
Tel-Aviv Sourasky Medical Center | |
Tel-Aviv, Israel | |
Italy | |
Monaldi Hospital, University of Naples S.U.N. | |
Naples, Italy | |
Agostino Gemelli Hospital | |
Rome, Italy |
Study Chair: | Johan Mouton, MD PhD | Radboud University Medical Center | |
Principal Investigator: | Mical Paul, MD | Rambam Health Care Centre |
Responsible Party: | Mical Paul, MD, Rabin Medical Center |
ClinicalTrials.gov Identifier: | NCT01732250 |
Other Study ID Numbers: |
0276-12-RMC |
First Posted: | November 22, 2012 Key Record Dates |
Last Update Posted: | April 12, 2017 |
Last Verified: | April 2017 |
Gram-Negative Bacterial Infections Resistant Bacteria Drug Resistance, Bacterial Colistin |
Bacterial Infections Gram-Negative Bacterial Infections Infections Bacterial Infections and Mycoses |
Meropenem Colistin Anti-Bacterial Agents Anti-Infective Agents |