<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04489459</url>
  </required_header>
  <id_info>
    <org_study_id>D12019</org_study_id>
    <nct_id>NCT04489459</nct_id>
  </id_info>
  <brief_title>Comparative Clinical Study Between Colistin-Tigecycline Combined Therapy Versus Colistin-Meropenem Combined Therapy in Treatment of Blood Stream Infections With Multidrug-Resistant Klebsiella Pneumoniae</brief_title>
  <official_title>Comparative Clinical Study Between Colistin-Tigecycline Combined Therapy Versus Colistin-Meropenem Combined Therapy in Treatment of Blood Stream Infections With Multidrug-Resistant Klebsiella Pneumoniae</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Al-Azhar University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Al-Azhar University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective, comparative study is evaluating the effectiveness and adverse effects of&#xD;
      using colistin at a loading dose of 9 million international units (MIU) followed by 4.5 MIU&#xD;
      every 12 h (q12 h) + tigecycline at a loading dose of 100 mg followed by 50 mg every 12 h&#xD;
      (q12 h) versus colistin + meropenem 2 g q8 h in treating blood stream infections due to&#xD;
      multidrug-resistant (MDR) Klebsiella pneumoniae. The aims of the current study are to&#xD;
      investigate and evaluate the therapeutic activity and side effects of Colistin-Meropenem&#xD;
      combined therapy versus Colistin-Tigecycline combined therapy in treatment of patients with&#xD;
      Multiple Drug Resistant (MDR)-Klebsiella pneumonia bacteraemia The primary goal is comparing&#xD;
      14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae&#xD;
      infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin -&#xD;
      meropenem combined therapies. The secondary goal is comparing the comorbidities&#xD;
      (nephrotoxicity, hepatotoxicity, neurotoxicity, hematological changes) between critically ill&#xD;
      patients with MDR Gram-negative Klebsiella pneumoniae infection who will be treated with&#xD;
      colistin - tigecycline versus colistin - meropenem combined therapies.&#xD;
&#xD;
      Method: A total of 60 patients were divided into two groups (30 patients each); the first&#xD;
      group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by&#xD;
      maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg&#xD;
      IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1&#xD;
      hour q12 and the second group received Intravenous colistin 9 MIU IV infusion over 2 hours&#xD;
      loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus&#xD;
      Intravenous meropenem 2 g IV infusion over 30 minutes q8 h&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">September 21, 2019</start_date>
  <completion_date type="Anticipated">July 2020</completion_date>
  <primary_completion_date type="Anticipated">July 2020</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>single-blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Comparing 14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin - meropenem combined therapies.</measure>
    <time_frame>7-14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparing comorbidities:nephrotoxicity,hepatotoxicity,neurotoxicity,hematological changes between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection treated with colistin-tigecycline vs colistin-meropenem</measure>
    <time_frame>7-14 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Treatment of Blood Stream Infections Due to Multidrug-Resistant Klebsiella Pneumoniae</condition>
  <arm_group>
    <arm_group_label>colistin-tigecycline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>this group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>colistin-meropenem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous meropenem 2 g IV infusion over 30 minutes q8 h</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colistin</intervention_name>
    <description>Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h</description>
    <arm_group_label>colistin-meropenem</arm_group_label>
    <arm_group_label>colistin-tigecycline</arm_group_label>
    <other_name>polymixin B</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Meropenem</intervention_name>
    <description>Intravenous meropenem 2 g IV infusion over 30 minutes q8 h</description>
    <arm_group_label>colistin-meropenem</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tigecycline</intervention_name>
    <description>Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12</description>
    <arm_group_label>colistin-tigecycline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with blood stream infection caused by MDR K. pneumoniae, as defined by&#xD;
             Infectious Diseases Society of America (IDSA), who were hospitalised in the general&#xD;
             ICU, confirmed with carbapenem-resistant K. pneumoniae-positive culture results from&#xD;
             blood sample within the previous 5 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All patients without a MDR carbapenem-resistant K. pneumoniae-positive culture&#xD;
             isolated from the blood. In addition, the following patients are excluded: patients&#xD;
             with a Glasgow Coma Scale (GCS) score of &lt;9 in non-ventilated patients or &lt;6 in&#xD;
             ventilated patients; patients with end-stage metastatic malignant cancer; and all&#xD;
             terminal patients with Acute Physiology and Chronic Health Evaluation (APACHE) II or&#xD;
             Sequential Organ Failure Assessment (SOFA) scores of &gt;34 or &gt;15, respectively, and&#xD;
             risk of mortality &gt;85% or &gt;80% on the first day of colistin administration,&#xD;
             respectively [27,28]. Moreover, patients who received i.v. colistin combination&#xD;
             therapies for &lt;72 h are excluded from further analysis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Salma Wagih Abdalla, Bachelor</last_name>
    <phone>00201100701178</phone>
    <email>salma9793@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Qasr El Ainy</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother. 2009 May;53(5):1868-73. doi: 10.1128/AAC.00782-08. Epub 2009 Feb 17.</citation>
    <PMID>19223638</PMID>
  </reference>
  <reference>
    <citation>Maltezou HC, Giakkoupi P, Maragos A, Bolikas M, Raftopoulos V, Papahatzaki H, Vrouhos G, Liakou V, Vatopoulos AC. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J Infect. 2009 Mar;58(3):213-9. doi: 10.1016/j.jinf.2009.01.010. Epub 2009 Feb 26.</citation>
    <PMID>19246099</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2020</study_first_posted>
  <last_update_submitted>July 27, 2020</last_update_submitted>
  <last_update_submitted_qc>July 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Al-Azhar University</investigator_affiliation>
    <investigator_full_name>Salma Wagih Abdalla</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>Colistin</keyword>
  <keyword>Tigecycline</keyword>
  <keyword>Meropenem</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Klebsiella Infections</mesh_term>
    <mesh_term>Sepsis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meropenem</mesh_term>
    <mesh_term>Colistin</mesh_term>
    <mesh_term>Tigecycline</mesh_term>
    <mesh_term>Polymyxins</mesh_term>
    <mesh_term>Polymyxin B</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04489459
org study id: D12019
nct id: NCT04489459
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This prospective, comparative study is evaluating the effectiveness and adverse effects of
      using colistin at a loading dose of 9 million international units (MIU) followed by 4.5 MIU
      every 12 h (q12 h) + tigecycline at a loading dose of 100 mg followed by 50 mg every 12 h
      (q12 h) versus colistin + meropenem 2 g q8 h in treating blood stream infections due to
      multidrug-resistant (MDR) Klebsiella pneumoniae. The aims of the current study are to
      investigate and evaluate the therapeutic activity and side effects of Colistin-Meropenem
      combined therapy versus Colistin-Tigecycline combined therapy in treatment of patients with
      Multiple Drug Resistant (MDR)-Klebsiella pneumonia bacteraemia The primary goal is comparing
      14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae
      infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin -
      meropenem combined therapies. The secondary goal is comparing the comorbidities
      (nephrotoxicity, hepatotoxicity, neurotoxicity, hematological changes) between critically ill
      patients with MDR Gram-negative Klebsiella pneumoniae infection who will be treated with
      colistin - tigecycline versus colistin - meropenem combined therapies.

      Method: A total of 60 patients were divided into two groups (30 patients each); the first
      group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by
      maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg
      IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1
      hour q12 and the second group received Intravenous colistin 9 MIU IV infusion over 2 hours
      loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus
      Intravenous meropenem 2 g IV infusion over 30 minutes q8 h
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
masking description: single-blind
measure: Comparing 14 day mortality between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection as evaluation of the therapeutic activity of colistin - tigecycline vs. colistin - meropenem combined therapies.
time frame: 7-14 days
measure: Comparing comorbidities:nephrotoxicity,hepatotoxicity,neurotoxicity,hematological changes between critically ill patients with MDR Gram-negative Klebsiella pneumoniae infection treated with colistin-tigecycline vs colistin-meropenem
time frame: 7-14 days
arm group label: colistin-tigecycline
arm group type: Active Comparator
description: this group received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12h
arm group label: colistin-meropenem
arm group type: Active Comparator
description: received Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h plus Intravenous meropenem 2 g IV infusion over 30 minutes q8 h
intervention type: Drug
intervention name: Colistin
description: Intravenous colistin 9 MIU IV infusion over 2 hours loading dose followed by maintenance dose 4.5 MIU IV infusion over 2 hours q12 h
arm group label: colistin-meropenem
arm group label: colistin-tigecycline
other name: polymixin B
intervention type: Drug
intervention name: Meropenem
description: Intravenous meropenem 2 g IV infusion over 30 minutes q8 h
arm group label: colistin-meropenem
intervention type: Drug
intervention name: Tigecycline
description: Intravenous Tigecycline 100 mg IV infusion over 1 hour loading dose followed by maintenance dose 50 mg IV infusion over 1 hour q12
arm group label: colistin-tigecycline
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Salma Wagih Abdalla, Bachelor
phone: 00201100701178
email: salma9793@gmail.com
facility: 
status: Recruiting
country: Egypt
citation: Daikos GL, Petrikkos P, Psichogiou M, Kosmidis C, Vryonis E, Skoutelis A, Georgousi K, Tzouvelekis LS, Tassios PT, Bamia C, Petrikkos G. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother. 2009 May;53(5):1868-73. doi: 10.1128/AAC.00782-08. Epub 2009 Feb 17.
PMID: 19223638
citation: Maltezou HC, Giakkoupi P, Maragos A, Bolikas M, Raftopoulos V, Papahatzaki H, Vrouhos G, Liakou V, Vatopoulos AC. Outbreak of infections due to KPC-2-producing Klebsiella pneumoniae in a hospital in Crete (Greece). J Infect. 2009 Mar;58(3):213-9. doi: 10.1016/j.jinf.2009.01.010. Epub 2009 Feb 26.
PMID: 19246099
responsible party type: Principal Investigator
investigator affiliation: Al-Azhar University
investigator full name: Salma Wagih Abdalla
investigator title: Principle Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Pneumonia
mesh term: Klebsiella Infections
mesh term: Sepsis
mesh term: Meropenem
mesh term: Colistin
mesh term: Tigecycline
mesh term: Polymyxins
mesh term: Polymyxin B
sharing ipd: Undecided