Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem - Full Text View

Purpose

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	Intervention	Phase
Gram-Negative Bacterial Infections	Drug: Colistin Drug: Meropenem	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem

Resource links provided by NLM:

MedlinePlus related topics: Bacterial Infections

Drug Information available for: Colistin Colistin sulfate Colistimethate sodium Meropenem

U.S. FDA Resources

Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:

Clinical success [ Time Frame: 14 days ] [ Designated as safety issue: No ]
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 [ Time Frame: 14 and 28 days ] [ Designated as safety issue: Yes ]
14 and 28-day all-cause mortality
Clinical success with modification [ Time Frame: 14 days ] [ Designated as safety issue: No ]
Clinical success, but with modification to the antibiotic treatment not permitted by protocol
Time to defervescence [ Time Frame: 28 days ] [ Designated as safety issue: No ]
defined as time to reach a temperature of <38°C with no recurrence for 3 days
Time to weaning [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Time to weaning from mechanical ventilation in VAP for patients weaned alive
Time to hospital discharge [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Time to hospital discharge for patient discharged alive
Microbiological failure [ Time Frame: 28 days ] [ Designated as safety issue: No ]
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. A repeat sputum/ tracheal aspirate culture will be obtain on day 7 from patients who were recruited with VAP or HAP
Superinfections [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days
New resistant infection [ Time Frame: 28 days ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test

Estimated Enrollment:	360
Study Start Date:	January 2013
Estimated Study Completion Date:	February 2016
Estimated Primary Completion Date:	January 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Colistimethate Sodium Coliracin 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	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: Colistimethate Sodium Coliracin

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
No more than 96 hours from time index culture was taken

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01732250

Contacts

Contact: Mical Paul, MD

paulm@post.tau.ac.il

Locations

Greece
Atikkon Hospital	Not yet recruiting
Athens, Greece
Contact: Diamantis Plachouras, MD
Principal Investigator: Diamantis Plachouras, MD PhD
Laikon Hosptial	Not yet recruiting
Athens, Greece
Contact: Diamantis Plachouras, MD PhD
Principal Investigator: Diamantis Plachouras, MD PhD
Israel
Rambam Health Care Center	Not yet recruiting
Haifa, Israel
Contact: Mical Paul, MD
Principal Investigator: Mical Paul, MD
Rabin Medical Center	Not yet recruiting
Petach-Tikvah, Israel
Contact: Leonard Leibovici, MD
Principal Investigator: Leonard Leibovici, MD
Tel-Aviv Sourasky Medical Center	Not yet recruiting
Tel-Aviv, Israel
Contact: Yehuda Carmeli, MD
Principal Investigator: Yehuda Carmeli, MD
Italy
Agostino Gemelli Hospital	Not yet recruiting
Rome, Italy
Contact: Giulia De Angelis, MD
Principal Investigator: Evelina Tacconelli, MD

Sponsors and Collaborators

michal paul

European Commission

Investigators

Study Chair:	Johan Mouton, MD PhD	Radboud University
Principal Investigator:	Mical Paul, MD	Rambam Health Care Centre

More Information

No publications provided

Responsible Party:	michal paul, MD, Rabin Medical Center
ClinicalTrials.gov Identifier:	NCT01732250 History of Changes
Other Study ID Numbers:	0276-12-RMC
Study First Received:	November 19, 2012
Last Updated:	November 21, 2012
Health Authority:	Israel: Ethics Commission Greece: Ethics Committee Italy: The Italian Medicines Agency

Keywords provided by Rabin Medical Center:

Gram-Negative Bacterial Infections
Resistant Bacteria
Drug Resistance, Bacterial
Colistin

Additional relevant MeSH terms:

Bacterial Infections
Gram-Negative Bacterial Infections
Colistin
Meropenem

Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013