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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
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Mical Paul, Rabin Medical Center

Tracking Information
First Submitted Date  ICMJE November 19, 2012
First Posted Date  ICMJE November 22, 2012
Last Update Posted Date April 12, 2017
Actual Study Start Date  ICMJE March 2013
Actual Primary Completion Date January 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2013)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2012)
  • Secondary outcomes and adverse events [ Time Frame: 14 and 28 days ]
    14 and 28-day all-cause mortality
  • 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. 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 ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
Official Title  ICMJE Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Gram-Negative Bacterial Infections
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
    Interventions:
    • Drug: Colistin
    • Drug: Meropenem
  • Active Comparator: Colistin
    IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function
    Intervention: Drug: Colistin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 10, 2017)
406
Original Estimated Enrollment  ICMJE
 (submitted: November 21, 2012)
360
Actual Study Completion Date  ICMJE February 28, 2017
Actual Primary Completion Date January 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Greece,   Israel,   Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01732250
Other Study ID Numbers  ICMJE 0276-12-RMC
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mical Paul, Rabin Medical Center
Study Sponsor  ICMJE Mical Paul
Collaborators  ICMJE European Commission
Investigators  ICMJE
Study Chair: Johan Mouton, MD PhD Radboud University
Principal Investigator: Mical Paul, MD Rambam Health Care Centre
PRS Account Rabin Medical Center
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP