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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Rabin Medical Center
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Mical Paul, Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT01732250
First received: November 19, 2012
Last updated: October 6, 2013
Last verified: October 2013
  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:


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.

    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 ] [ 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.

    • 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 ] [ 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: March 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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Recruiting
Athens, Greece
Contact: Diamantis Plachouras, MD         
Principal Investigator: Diamantis Plachouras, MD PhD         
Laikon Hosptial Recruiting
Athens, Greece
Contact: Diamantis Plachouras, MD PhD         
Principal Investigator: Diamantis Plachouras, MD PhD         
Israel
Rambam Health Care Center Recruiting
Haifa, Israel
Contact: Mical Paul, MD         
Principal Investigator: Mical Paul, MD         
Rabin Medical Center Recruiting
Petach-Tikvah, Israel
Contact: Leonard Leibovici, MD         
Principal Investigator: Leonard Leibovici, MD         
Tel-Aviv Sourasky Medical Center Recruiting
Tel-Aviv, Israel
Contact: Yehuda Carmeli, MD         
Principal Investigator: Yehuda Carmeli, MD         
Italy
Agostino Gemelli Hospital Terminated
Rome, Italy
Sponsors and Collaborators
Mical 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: Mical 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: October 6, 2013
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
Infection
Colistin
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014