<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/NCT04502381</url>
  </required_header>
  <id_info>
    <org_study_id>NK/6146/DM/452</org_study_id>
    <nct_id>NCT04502381</nct_id>
  </id_info>
  <brief_title>Combined Inhalational With Intravenous Amphotericin B Versus Intravenous Amphotericin B Alone for Pulmonary Mucormycosis</brief_title>
  <official_title>A Randomized Controlled Trial of Combined Inhalational With Intravenous Amphotericin B in Comparison With Intravenous Amphotericin B Alone for Treatment of Pulmonary Mucormycosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Postgraduate Institute of Medical Education and Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Postgraduate Institute of Medical Education and Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the safety and feasibility of combined inhalational and intravenous amphotericin B&#xD;
      therapy for the treatment of pulmonary mucormycosis. And compare the efficacy of combined&#xD;
      therapy with that of intravenous amphotericin B alone.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pulmonary mucormycosis is a relatively a rare disease with a high mortality. The&#xD;
      angioinvasion associated with mucormycosis prevents efficient drug delivery at the diseased&#xD;
      site. Inhaled amphotericin B achieves drug levels in lung tissue and has been shown to be&#xD;
      useful in several diseases including chronic pulmonary and allergic bronchopulmonary&#xD;
      aspergillosis. Further inhaled forms of amphotericin B are associated with less&#xD;
      nephrotoxicity and other systemic adverse effects. The role of inhaled amphotericin B in&#xD;
      pulmonary mucormycosis has been previously demonstrated in murine models and anecdotal&#xD;
      reports. The study hypothesis is that combined therapy with inhalational and intravenous&#xD;
      amphotericin B is likely to result in better outcomes as compared with intravenous&#xD;
      amphotericin B alone for treatment of pulmonary mucormycosis&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Actual">December 30, 2021</completion_date>
  <primary_completion_date type="Actual">October 30, 2021</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response (clinical and radiological improvement) at the end of six weeks of start of therapy</measure>
    <time_frame>6 weeks after the start of therapy</time_frame>
    <description>Complete response: Survival and resolution of all attributable symptoms and signs of disease plus Resolution of radiological lesion(s); persistence of only a scar or postoperative changes can be equated with complete radiological response Partial response: Survival and improvement of attributable symptoms and signs of disease plus At least 25% reduction in diameter of radiological lesion OR In cases of radiological stabilization (defined as 0%-25% reduction in the diameter), resolution of all attributable symptoms and signs of fungal disease can be equated with a partial response Stable response: Survival and minor or no improvement in attributable symptoms and signs; plus Radiological stabilization (defined as 0%-25% reduction in diameter) Progression: Worsening clinical symptoms or signs plus New sites of disease or radiological worsening Death Complete and partial response will be called &quot;success&quot;</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse events related to therapy</measure>
    <time_frame>till 6 weeks from randomization (start of therapy)</time_frame>
    <description>Adverse events related to therapy (especially, incidence of bronchospasm and acute kidney injury)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>During hospital stay, approximately till 6 weeks from randomization (start of therapy)</time_frame>
    <description>Death due to any cause in-hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>90 day mortality</measure>
    <time_frame>90 days from the date of randomization</time_frame>
    <description>Death due to any cause till 90 days of randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects requiring discontinuation or modification of therapy due to adverse events</measure>
    <time_frame>till 6 weeks from randomization (start of therapy)</time_frame>
    <description>Number of participants withdrawing therapy in each arm, divided by the total number of patients in the same arm</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Pulmonary Mucormycosis</condition>
  <arm_group>
    <arm_group_label>Intervention arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The study participants in the intervention arm will receive nebulization with amphotericin B deoxycholate (10 mg twice a day every alternate day, as described below) along with intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional arm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive treatment with only intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled amp B deoxycholate+intravenous liposomal amp B</intervention_name>
    <description>Intravenous liposomal amphotericin B (beginning with 3mg/kg) along with inhaled amphotericin as below: Amp-B deoxycholate 50 mg (Amphotret™ Bharat serums and vaccines limited), will be dissolved in 10 mL distilled water. 2 mL of the reconstituted amphotericin B solution will be transferred into the drug chamber of a breath actuated nebulizer (Lupineb Ultra kit breath actuated nebulize which contains aeroclipse XL Reusable Breath Actuated Nebulizer and DeVilbiss 3655 compressor). 3 mL of distilled water is added to 2 mL of the reconstituted amphotericin B. The nebulization is continued till the chamber is emptied of the drug or the patient does not tolerate the therapy.&#xD;
The first three doses of amphotericin B nebulization will be under the direct supervision of a physician. If tolerated, nebulization will be continued twice a day till tolerated or till response.The patient will complete a VAS score for cough after nebulization.</description>
    <arm_group_label>Intervention arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Intravenous liposomal amphotericin B alone</intervention_name>
    <description>Intravenous liposomal amphotericin B (beginning with 3mg/kg, up to 5 mg/kg), with or without surgery or other antifungals as clinically indicated</description>
    <arm_group_label>Conventional arm</arm_group_label>
    <arm_group_label>Intervention arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects with a clinicoradiologic suspicion of pulmonary mucormycosis will be enrolled if&#xD;
        the diagnosis of mucormycosis is pathologically or microbiologically (smear showing&#xD;
        aseptate hyphae, culture or molecular evidence showing Mucorales) confirmed. Cases of&#xD;
        disseminated mucormycosis will be included, only if the pulmonary infection is confirmed&#xD;
        pathologically or microbiologically from respiratory secretions or biopsy samples&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lack of informed consent&#xD;
&#xD;
          -  Hypersensitivity to amphotericin B or any component of the formulation&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  High likelihood of death within 48 h of enrolment&#xD;
&#xD;
          -  Suspected pulmonary mucormycosis without histological or microbiologic proof&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ratnakara Rao, MBBS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Postgraduate Institute of Medical Education and Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Post graduate Institute medical education and research</name>
      <address>
        <city>Chandigarh</city>
        <zip>160012</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>August 1, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>January 24, 2022</last_update_submitted>
  <last_update_submitted_qc>January 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Postgraduate Institute of Medical Education and Research</investigator_affiliation>
    <investigator_full_name>Ritesh Agarwal</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mucormycosis</mesh_term>
    <mesh_term>Zygomycosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amphotericin B</mesh_term>
    <mesh_term>Liposomal amphotericin B</mesh_term>
    <mesh_term>Deoxycholic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04502381
org study id: NK/6146/DM/452
nct id: NCT04502381
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To assess the safety and feasibility of combined inhalational and intravenous amphotericin B
      therapy for the treatment of pulmonary mucormycosis. And compare the efficacy of combined
      therapy with that of intravenous amphotericin B alone.
Pulmonary mucormycosis is a relatively a rare disease with a high mortality. The
      angioinvasion associated with mucormycosis prevents efficient drug delivery at the diseased
      site. Inhaled amphotericin B achieves drug levels in lung tissue and has been shown to be
      useful in several diseases including chronic pulmonary and allergic bronchopulmonary
      aspergillosis. Further inhaled forms of amphotericin B are associated with less
      nephrotoxicity and other systemic adverse effects. The role of inhaled amphotericin B in
      pulmonary mucormycosis has been previously demonstrated in murine models and anecdotal
      reports. The study hypothesis is that combined therapy with inhalational and intravenous
      amphotericin B is likely to result in better outcomes as compared with intravenous
      amphotericin B alone for treatment of pulmonary mucormycosis
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response (clinical and radiological improvement) at the end of six weeks of start of therapy
time frame: 6 weeks after the start of therapy
description: Complete response: Survival and resolution of all attributable symptoms and signs of disease plus Resolution of radiological lesion(s); persistence of only a scar or postoperative changes can be equated with complete radiological response Partial response: Survival and improvement of attributable symptoms and signs of disease plus At least 25% reduction in diameter of radiological lesion OR In cases of radiological stabilization (defined as 0%-25% reduction in the diameter), resolution of all attributable symptoms and signs of fungal disease can be equated with a partial response Stable response: Survival and minor or no improvement in attributable symptoms and signs; plus Radiological stabilization (defined as 0%-25% reduction in diameter) Progression: Worsening clinical symptoms or signs plus New sites of disease or radiological worsening Death Complete and partial response will be called "success"
measure: Adverse events related to therapy
time frame: till 6 weeks from randomization (start of therapy)
description: Adverse events related to therapy (especially, incidence of bronchospasm and acute kidney injury)
measure: In-hospital mortality
time frame: During hospital stay, approximately till 6 weeks from randomization (start of therapy)
description: Death due to any cause in-hospital
measure: 90 day mortality
time frame: 90 days from the date of randomization
description: Death due to any cause till 90 days of randomization
measure: Proportion of subjects requiring discontinuation or modification of therapy due to adverse events
time frame: till 6 weeks from randomization (start of therapy)
description: Number of participants withdrawing therapy in each arm, divided by the total number of patients in the same arm
arm group label: Intervention arm
arm group type: Experimental
description: The study participants in the intervention arm will receive nebulization with amphotericin B deoxycholate (10 mg twice a day every alternate day, as described below) along with intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)
arm group label: Conventional arm
arm group type: Active Comparator
description: Participants will receive treatment with only intravenous liposomal amphotericin B (3 to 5 mg/kg body weight)
intervention type: Drug
intervention name: Inhaled amp B deoxycholate+intravenous liposomal amp B
description: Intravenous liposomal amphotericin B (beginning with 3mg/kg) along with inhaled amphotericin as below: Amp-B deoxycholate 50 mg (Amphotret™ Bharat serums and vaccines limited), will be dissolved in 10 mL distilled water. 2 mL of the reconstituted amphotericin B solution will be transferred into the drug chamber of a breath actuated nebulizer (Lupineb Ultra kit breath actuated nebulize which contains aeroclipse XL Reusable Breath Actuated Nebulizer and DeVilbiss 3655 compressor). 3 mL of distilled water is added to 2 mL of the reconstituted amphotericin B. The nebulization is continued till the chamber is emptied of the drug or the patient does not tolerate the therapy.
The first three doses of amphotericin B nebulization will be under the direct supervision of a physician. If tolerated, nebulization will be continued twice a day till tolerated or till response.The patient will complete a VAS score for cough after nebulization.
arm group label: Intervention arm
intervention type: Drug
intervention name: Intravenous liposomal amphotericin B alone
description: Intravenous liposomal amphotericin B (beginning with 3mg/kg, up to 5 mg/kg), with or without surgery or other antifungals as clinically indicated
arm group label: Conventional arm
arm group label: Intervention arm
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Ratnakara Rao, MBBS, MD
role: Principal Investigator
affiliation: Postgraduate Institute of Medical Education and Research
facility: 
country: India
responsible party type: Principal Investigator
investigator affiliation: Postgraduate Institute of Medical Education and Research
investigator full name: Ritesh Agarwal
investigator title: Professor
mesh term: Mucormycosis
mesh term: Zygomycosis
mesh term: Amphotericin B
mesh term: Liposomal amphotericin B
mesh term: Deoxycholic Acid
sharing ipd: No