<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/NCT02218359</url>
  </required_header>
  <id_info>
    <org_study_id>CAP-01-103</org_study_id>
    <nct_id>NCT02218359</nct_id>
  </id_info>
  <brief_title>Aerosolized Amikacin and Fosfomycin in Mechanically Ventilated Patients With Gram-negative and / or Gram-positive Bacterial Colonization</brief_title>
  <official_title>A Randomized Double-Blind, Placebo-Controlled, Crossover to Open Label, Phase 2 Study of Aerosolized Amikacin and Fosfomycin Delivered Via the Investigational eFlow® AFIS Inline System in Mechanically Ventilated Patients With Gram-negative and/or Gram-positive Bacterial Colonization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cardeas Pharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cardeas Pharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin&#xD;
      Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with&#xD;
      Gram-negative and / or Gram-positive bacterial colonization.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin&#xD;
      fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution (AMS) and fosfomycin&#xD;
      solution (FFS), delivered by aerosol to the lungs via the Investigational eFlow AFIS Inline&#xD;
      System (AFIS Inline System) with tamper evident reservoir. Patients will be randomized to&#xD;
      receive 5 days of treatment with either AFIS or placebo, followed by all patients receiving&#xD;
      open label AFIS for five days. The primary efficacy endpoint is the change from baseline in&#xD;
      tracheal aspirate Gram-negative and/or Gram-positive bacterial density at the end of the&#xD;
      5-day randomized course of study drug.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No Participants Enrolled&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">January 2016</completion_date>
  <primary_completion_date type="Anticipated">December 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density</measure>
    <time_frame>5 day randomized course of study drug</time_frame>
    <description>Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density at the end of the 5-day randomized course of study drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Microbiological response rate in patients with multidrug resistant Gram-negative bacteria</measure>
    <time_frame>Day 5</time_frame>
    <description>Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for multidrug resistant (MDR) Gram-negative bacteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eradication of bacteria</measure>
    <time_frame>Days 10, 21, and 28</time_frame>
    <description>Eradication of bacteria at Days 10, 21, and 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical worsening</measure>
    <time_frame>Day 1 - Day 28</time_frame>
    <description>Clinical worsening (defined as requiring institution of IV antibiotics) from Day 1 through Day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiological response rates</measure>
    <time_frame>Day 10</time_frame>
    <description>Microbiological response rates at Day 10 in all patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiological response rates in patients with MRSA</measure>
    <time_frame>Day 5</time_frame>
    <description>Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for methicillin resistant Staphylococcus aureus (MRSA)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Pneumonia, Bacterial</condition>
  <arm_group>
    <arm_group_label>Amikacin Fosfomycin Inhalation Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS Inline System.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aerosolized Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Aerosolized placebo to be administered by aerosol using the AFIS Inline System.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amikacin Fosfomycin Inhalation Solution</intervention_name>
    <description>300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the AFIS Inline System</description>
    <arm_group_label>Amikacin Fosfomycin Inhalation Solution</arm_group_label>
    <other_name>Amikacin Fosfomycin Inhalation System (AFIS)</other_name>
    <other_name>eFlow Inline System</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aerosolized placebo</intervention_name>
    <description>Placebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System.</description>
    <arm_group_label>Aerosolized Placebo</arm_group_label>
    <other_name>eFlow Inline System</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amikacin Fosfomycin Inhalation Solution</intervention_name>
    <description>Open-label crossover for all patients Days 6-10</description>
    <arm_group_label>Aerosolized Placebo</arm_group_label>
    <arm_group_label>Amikacin Fosfomycin Inhalation Solution</arm_group_label>
    <other_name>Amikacin Fosfomycin Inhalation System (AFIS)</other_name>
    <other_name>eFlow Inline System</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and non-pregnant, non-lactating females, ≥ 18 years and ≤ 80 years of age&#xD;
&#xD;
          -  Intubated and mechanically-ventilated&#xD;
&#xD;
          -  Presence of Gram-negative and/or Gram-positive organism(s) by culture of respiratory&#xD;
             secretions from a sample obtained within the previous 7 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitivity to amikacin or fosfomycin.&#xD;
&#xD;
          -  Diagnosis of pneumonia, defined as presence of a new or progressive infiltrate(s) on&#xD;
             chest radiograph (within 7 days prior to screening), as determined by the treating&#xD;
             physician&#xD;
&#xD;
          -  Use of systemic antibiotics with efficacy against likely respiratory tract pathogens&#xD;
             at the time of randomization&#xD;
&#xD;
          -  Severe acute respiratory distress syndrome (defined as PaO2/FiO2 ≤ 100 mmHg and&#xD;
             diffuse infiltrates on Chest X-ray)&#xD;
&#xD;
          -  Refractory septic shock (severe sepsis plus unstable hypotension, in spite of adequate&#xD;
             fluid resuscitation and vasopressors)&#xD;
&#xD;
          -  Evidence of significant renal impairment (serum creatinine &gt; 4.0 mg/dL within 24 hours&#xD;
             prior to screening) . If serum creatinine is &gt; 2.0 mg/dL, site must be capable of&#xD;
             performing continuous renal replacement therapy, if clinically indicated. Patients&#xD;
             with serum creatinine &gt; 4.0 mg/dL and being treated with continuous renal replacement&#xD;
             therapy (continuous venous-venous hemofiltration or continuous venous-venous&#xD;
             hemodialysis) or chronic hemodialysis are eligible&#xD;
&#xD;
          -  Evidence of ototoxicity (history of hearing aid use prior to current hospitalization)&#xD;
&#xD;
          -  Evidence of hepatotoxicity (alanine aminotransferase [ALT] or aspartate&#xD;
             aminotransferase [AST] &gt; 3X the upper limit of normal value within 24 hours prior to&#xD;
             screening)&#xD;
&#xD;
          -  Any of the following conditions that interfere with the assessment or interpretation&#xD;
             of the diagnosis or response to therapy: chest trauma with loss of stability of the&#xD;
             thoracic cage following a fracture of the sternum, ribs, or both; increased amounts of&#xD;
             fluid in the lung cavities requiring chest tube drainage; lung cancer within the last&#xD;
             2 years; lung abscess(s); anatomical bronchial obstruction; suspected atypical&#xD;
             pneumonia; chemical pneumonitis (e.g., inhalation injury); cystic fibrosis; congestive&#xD;
             heart failure (leading to a PaO2/FiO2 ratio ≤ 100 mmHg and diffuse infiltrates on&#xD;
             Chest X-ray)&#xD;
&#xD;
          -  Immunocompromised patients, including those with neutropenia NOT due to the current&#xD;
             infection (absolute neutrophil count &lt; 500/mm³), leukemia, lymphoma, human&#xD;
             immunodeficiency virus (HIV) infection with CD4 count &lt; 200 cells/mm3, or splenectomy;&#xD;
             those who are early post-transplantation, are on cytotoxic chemotherapy, or are on&#xD;
             high-dose steroids (e.g., &gt; 40 mg of prednisone or its equivalent [&gt; 160 mg&#xD;
             hydrocortisone, &gt; 32 mg methylprednisolone, &gt; 6 mg dexamethasone, &gt; 200 mg cortisone]&#xD;
             daily for &gt; 2 weeks)&#xD;
&#xD;
          -  Positive urine and/or serum beta-hCG pregnancy test (only in women of reproductive&#xD;
             age)&#xD;
&#xD;
          -  Participating in or has participated in other investigational interventional studies&#xD;
             (drug or device) within the last 30 days (or 5 times the half-life of the previously&#xD;
             administered investigational compound, whichever is longer) prior to study treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce Montgomery, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Cardeas Pharma</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://www.nlm.nih.gov/medlineplus/antibiotics.html</url>
    <description>MedlinePlus related topics: Antibiotics</description>
  </link>
  <link>
    <url>http://www.nlm.nih.gov/medlineplus/pneumonia.html</url>
    <description>MedlinePlus related topics: Pneumonia</description>
  </link>
  <link>
    <url>http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&amp;objectHandle=DBMaint&amp;APPLICATION_NAME=drugportal&amp;actionHandle=default&amp;nextPage=jsp/drugportal/ResultScreen.jsp&amp;TXTSUPERLISTID=0037517285&amp;QV1=AMIKACIN</url>
    <description>Drug Information available for amikacin</description>
  </link>
  <link>
    <url>http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&amp;objectHandle=DBMaint&amp;APPLICATION_NAME=drugportal&amp;actionHandle=default&amp;nextPage=jsp/drugportal/ResultScreen.jsp&amp;TXTSUPERLISTID=0023155024&amp;QV1=FOSFOMYCIN</url>
    <description>Drug information available for fosfomycin</description>
  </link>
  <link>
    <url>http://www.clinicaltrials.gov/ct2/info/fdalinks</url>
    <description>U.S. FDA Resources</description>
  </link>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 18, 2014</study_first_posted>
  <last_update_submitted>November 16, 2015</last_update_submitted>
  <last_update_submitted_qc>November 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 18, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gram-negative pneumonia</keyword>
  <keyword>Aerosol antibiotics</keyword>
  <keyword>Mechanical ventilation</keyword>
  <keyword>Amikacin</keyword>
  <keyword>Fosfomycin</keyword>
  <keyword>Pneumonia, Bacterial</keyword>
  <keyword>Pneumonia</keyword>
  <keyword>Bacterial Infections</keyword>
  <keyword>Lung Diseases</keyword>
  <keyword>Respiratory Tract Diseases</keyword>
  <keyword>Respiratory Tract Infections</keyword>
  <keyword>Anti-Bacterial Agents</keyword>
  <keyword>Anti-Infective Agents</keyword>
  <keyword>Therapeutic Uses</keyword>
  <keyword>Pharmacologic Actions</keyword>
  <keyword>MRSA</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Bacterial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amikacin</mesh_term>
    <mesh_term>Fosfomycin</mesh_term>
    <mesh_term>Pharmaceutical Solutions</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02218359
org study id: CAP-01-103
nct id: NCT02218359
lead sponsor: 
has dmc: No
To demonstrate the safety and efficacy of adjunctive therapy with the Amikacin Fosfomycin
      Inhalation System (AFIS) versus aerosolized placebo in mechanically ventilated patients with
      Gram-negative and / or Gram-positive bacterial colonization.
The primary purpose of this study is to demonstrate the safety and efficacy of the amikacin
      fosfomycin inhalation system (AFIS). AFIS consists of amikacin solution (AMS) and fosfomycin
      solution (FFS), delivered by aerosol to the lungs via the Investigational eFlow AFIS Inline
      System (AFIS Inline System) with tamper evident reservoir. Patients will be randomized to
      receive 5 days of treatment with either AFIS or placebo, followed by all patients receiving
      open label AFIS for five days. The primary efficacy endpoint is the change from baseline in
      tracheal aspirate Gram-negative and/or Gram-positive bacterial density at the end of the
      5-day randomized course of study drug.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density
time frame: 5 day randomized course of study drug
description: Change from baseline in tracheal aspirate Gram-negative and Gram-positive bacterial density at the end of the 5-day randomized course of study drug
measure: Microbiological response rate in patients with multidrug resistant Gram-negative bacteria
time frame: Day 5
description: Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for multidrug resistant (MDR) Gram-negative bacteria
measure: Eradication of bacteria
time frame: Days 10, 21, and 28
description: Eradication of bacteria at Days 10, 21, and 28
measure: Clinical worsening
time frame: Day 1 - Day 28
description: Clinical worsening (defined as requiring institution of IV antibiotics) from Day 1 through Day 28
measure: Microbiological response rates
time frame: Day 10
description: Microbiological response rates at Day 10 in all patients
measure: Microbiological response rates in patients with MRSA
time frame: Day 5
description: Microbiological response rates at Day 5 in patients whose pre-study treatment tracheal aspirate culture was positive for methicillin resistant Staphylococcus aureus (MRSA)
arm group label: Amikacin Fosfomycin Inhalation Solution
arm group type: Experimental
description: 300 mg of amikacin and 120 mg of fosfomycin to be administered by aerosol via the AFIS Inline System.
arm group label: Aerosolized Placebo
arm group type: Placebo Comparator
description: Aerosolized placebo to be administered by aerosol using the AFIS Inline System.
intervention type: Drug
intervention name: Amikacin Fosfomycin Inhalation Solution
description: 300 mg of amikacin and 120 mg of fosfomycin twice daily for 10 days to be administered by aerosol via the AFIS Inline System
arm group label: Amikacin Fosfomycin Inhalation Solution
other name: Amikacin Fosfomycin Inhalation System (AFIS)
other name: eFlow Inline System
intervention type: Drug
intervention name: Aerosolized placebo
description: Placebo twice daily for Days 1 -5 to be administered by aerosol using the eFlow Inline System.
arm group label: Aerosolized Placebo
other name: eFlow Inline System
intervention type: Drug
intervention name: Amikacin Fosfomycin Inhalation Solution
description: Open-label crossover for all patients Days 6-10
arm group label: Aerosolized Placebo
arm group label: Amikacin Fosfomycin Inhalation Solution
other name: Amikacin Fosfomycin Inhalation System (AFIS)
other name: eFlow Inline System
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Bruce Montgomery, M.D.
role: Study Director
affiliation: Cardeas Pharma
country: United States
url: http://www.nlm.nih.gov/medlineplus/antibiotics.html
description: MedlinePlus related topics: Antibiotics
url: http://www.nlm.nih.gov/medlineplus/pneumonia.html
description: MedlinePlus related topics: Pneumonia
url: http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0037517285&QV1=AMIKACIN
description: Drug Information available for amikacin
url: http://druginfo.nlm.nih.gov/drugportal/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=drugportal&actionHandle=default&nextPage=jsp/drugportal/ResultScreen.jsp&TXTSUPERLISTID=0023155024&QV1=FOSFOMYCIN
description: Drug information available for fosfomycin
url: http://www.clinicaltrials.gov/ct2/info/fdalinks
description: U.S. FDA Resources
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Pneumonia, Bacterial
mesh term: Amikacin
mesh term: Fosfomycin
mesh term: Pharmaceutical Solutions