<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/NCT02226705</url>
  </required_header>
  <id_info>
    <org_study_id>P110151</org_study_id>
    <nct_id>NCT02226705</nct_id>
  </id_info>
  <brief_title>Endoscopic Surgical Treatment of Rhino-Sinusal Mucormycosis</brief_title>
  <acronym>MICCA</acronym>
  <official_title>Treatment of Rhino-Sinusal Mucormycosis Through Transnasal Endoscopic Surgery Extended to the Skull Base.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Radical endoscopic transnasal surgery associated with medical treatment with liposomal&#xD;
      amphotericine B may increase the local control of Rhino-Sinusal Mucormycosis and the survival&#xD;
      rate. The objective of this study is to evaluate the local control rate and survival rate at&#xD;
      3 months after radical endoscopic transnasal surgery extended towards the skull base in&#xD;
      association with antifungal therapy and early surgical reevaluation of the extent of the&#xD;
      disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction : Treatment of Rhino-Sinusal Mucormycosis remains a challenge because of the&#xD;
      severity of the disease with high mortality rates. Mainly involving diabetic and&#xD;
      immunodeficient patients, first clinical presentation is a common infection of the sinuses&#xD;
      which can extend towards deep spaces of the face, orbits, the skull base and the brain. The&#xD;
      mortality rates range from 20 to 50%, up to 80% in case of cerebral extension. through&#xD;
      Transnasal Endoscopic Surgery extended to the Skull Base.&#xD;
&#xD;
      Hypothesis : We hypothesize that infected tissues are devascularized and because of that&#xD;
      antifungal therapies can hardly reach areas of infected tissues. Radical endoscopic&#xD;
      transnasal surgery associated with medical treatment with liposomal amphotericine B may&#xD;
      increase the local control of the disease and the survival rate. Clinical evaluation of the&#xD;
      extent of the disease within the first 7 days following initial surgery may represent a&#xD;
      prognosis factor.&#xD;
&#xD;
      Methods :&#xD;
&#xD;
      First national mutlicentric and multidisciplinary cohort on Rhino-Sinusal Mucormycosis&#xD;
      Radiological staging for evaluation of the extent of the disease using CT scan, MRI and PET&#xD;
      Scan at initial stage before surgery Radical surgery and/or endoscopic transnasal surgery&#xD;
      extended towards the skull base associated with liposomal amphotericine B medical treatment.&#xD;
&#xD;
      At day 7 new radiological evaluation and second surgical look to adapt surgical resection of&#xD;
      infected tissues, perform biopsies to search for mycormycosis, biofilms and dosage of the&#xD;
      concentration of liposomal amphotericin B inside tissues. New radiological and surgical looks&#xD;
      in case of absence of local control obtained on the second look and further.&#xD;
&#xD;
      Study of the response rate by an endoscopic &amp; scan follow-up (with biopsies for&#xD;
      anatomopathological et mycological studies) at 1 month, 3 months, 6 months &amp; one year. PET&#xD;
      scan initially &amp; at 3 months.&#xD;
&#xD;
      Number of subjects included : Phase II type trial (exclusion of a zero hypothesis of survival&#xD;
      rate &lt;50% ), N= 23 patients&#xD;
&#xD;
      Total length of the study 4 years Inclusion period time : 3 years Time of participation per&#xD;
      patient : 1 year Number of center and/or participating departments: 24 Mean number of&#xD;
      patients included per year and per center : 0 to 3 patients&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    End of inclusion period&#xD;
  </why_stopped>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">January 2021</completion_date>
  <primary_completion_date type="Actual">June 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Endoscopic surgical treatment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Local control rate and survival rate</measure>
    <time_frame>3 months</time_frame>
    <description>To evaluate the local control rate and survival rate at 3 months after radical endoscopic transnasal surgery extended towards the skull base in association with antifungal therapy and early surgical reevaluation of the extent of the disease.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival rates</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>Survival rates at 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Study of the response rate</measure>
    <time_frame>1 and 3 months</time_frame>
    <description>Study of the response rate at 1 and 3 months according to Segar criteria (Segal, Clin Infect Dis) using clinical, mycological and radiological evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Study of the local control</measure>
    <time_frame>3 months</time_frame>
    <description>Study of the local control obtained at day 7+/-5 days and survival rate and response rate at 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Study of the association between local control and survival rate and response rate</measure>
    <time_frame>3 months</time_frame>
    <description>Study of the association between local control obtained at 1 month and survival rate and response rate at 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluation of the interest of CT PET scan</measure>
    <time_frame>3 months</time_frame>
    <description>Evaluation of the interest of CT PET scan in studying clinical response at 3 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological staging</measure>
    <time_frame>3 months</time_frame>
    <description>Radiological staging: comparison of the initial extent of the mucormycosis at day 0 by CT scan and MRI and survival rate at 3 months and local control obtained at day 7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dosage of the amphotericin B concentration inside tissues</measure>
    <time_frame>Day 7</time_frame>
    <description>Dosage of the amphotericin B concentration inside tissues (infeusingcted and at the border of infected tissues) as obtained with biopsies at day 7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Search for biofilms using confocal microscopy</measure>
    <time_frame>Day 0 and Day 7</time_frame>
    <description>Search for biofilms using confocal microscopy on infected tissues biopsies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Staging of sequellae</measure>
    <time_frame>3 months, 6 months and 1 year</time_frame>
    <description>Staging of sequellae using quality of life questionnaires</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bank of mucormycosis tissues</measure>
    <time_frame>Day 0, Day 7, Day 14, D21 and Day 28</time_frame>
    <description>Bank of mucormycosis tissues at -80°C</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Rhinocerebral Mucormycosis</condition>
  <arm_group>
    <arm_group_label>Multiple Surgeries</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergoing transnasal endoscopic surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Multiple transnasal endoscopic surgeries</intervention_name>
    <description>Transnasal endoscopic surgery extended to the skull base</description>
    <arm_group_label>Multiple Surgeries</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Man or woman, over 18 years old, presenting a mucormycosis on a sinus biopsy showing&#xD;
             large filaments with non or little septae compatible with a mucoral or with a positive&#xD;
             culture for a mucoral on a sinus sample associated to clinical head &amp; neack anomalies&#xD;
             (endoscopic) &amp; scans compatible with a mucormycosis previous to the inclusion and this&#xD;
             whatever the patient incumbent pathology.&#xD;
&#xD;
          -  Patient treated by liposomal amphotericin B or just before being treated&#xD;
&#xD;
          -  Signature of informed consent :&#xD;
&#xD;
               -  by the patient if he is able to express their will&#xD;
&#xD;
               -  by the family or close, if the patient is unable to consent&#xD;
&#xD;
          -  Inclusion in emergency clause is possible ( CPP agreement ) if the patient is&#xD;
             incapacitated , no close is present and that the surgery is urgent&#xD;
&#xD;
          -  Person affiliated to a Health Security System (beneficiary)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, breastfeeding&#xD;
&#xD;
          -  Disseminated Mucormycosis (involvment of one site distant from the head and neck)&#xD;
&#xD;
          -  Known hypersensitivity to a polyene&#xD;
&#xD;
          -  Absence of documentation of mucormycosis (histological, mycological)&#xD;
&#xD;
          -  Contraindication to the completion of the surgery as provided in this protocol&#xD;
&#xD;
          -  Patient is the subject of a guardianship or tutelage measure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Romain KANIA, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistance Publique - Hôpitaux de Paris</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hôpital Lariboisière</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 25, 2014</study_first_submitted>
  <study_first_submitted_qc>August 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2014</study_first_posted>
  <last_update_submitted>April 8, 2021</last_update_submitted>
  <last_update_submitted_qc>April 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rhinocerebral Mucormycosis</keyword>
  <keyword>Surgery</keyword>
  <keyword>Fungal Infection</keyword>
  <keyword>Survival</keyword>
  <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>
  <!-- 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/NCT02226705
org study id: P110151
nct id: NCT02226705
lead sponsor: 
has dmc: No
Radical endoscopic transnasal surgery associated with medical treatment with liposomal
      amphotericine B may increase the local control of Rhino-Sinusal Mucormycosis and the survival
      rate. The objective of this study is to evaluate the local control rate and survival rate at
      3 months after radical endoscopic transnasal surgery extended towards the skull base in
      association with antifungal therapy and early surgical reevaluation of the extent of the
      disease.
Introduction : Treatment of Rhino-Sinusal Mucormycosis remains a challenge because of the
      severity of the disease with high mortality rates. Mainly involving diabetic and
      immunodeficient patients, first clinical presentation is a common infection of the sinuses
      which can extend towards deep spaces of the face, orbits, the skull base and the brain. The
      mortality rates range from 20 to 50%, up to 80% in case of cerebral extension. through
      Transnasal Endoscopic Surgery extended to the Skull Base.

      Hypothesis : We hypothesize that infected tissues are devascularized and because of that
      antifungal therapies can hardly reach areas of infected tissues. Radical endoscopic
      transnasal surgery associated with medical treatment with liposomal amphotericine B may
      increase the local control of the disease and the survival rate. Clinical evaluation of the
      extent of the disease within the first 7 days following initial surgery may represent a
      prognosis factor.

      Methods :

      First national mutlicentric and multidisciplinary cohort on Rhino-Sinusal Mucormycosis
      Radiological staging for evaluation of the extent of the disease using CT scan, MRI and PET
      Scan at initial stage before surgery Radical surgery and/or endoscopic transnasal surgery
      extended towards the skull base associated with liposomal amphotericine B medical treatment.

      At day 7 new radiological evaluation and second surgical look to adapt surgical resection of
      infected tissues, perform biopsies to search for mycormycosis, biofilms and dosage of the
      concentration of liposomal amphotericin B inside tissues. New radiological and surgical looks
      in case of absence of local control obtained on the second look and further.

      Study of the response rate by an endoscopic & scan follow-up (with biopsies for
      anatomopathological et mycological studies) at 1 month, 3 months, 6 months & one year. PET
      scan initially & at 3 months.

      Number of subjects included : Phase II type trial (exclusion of a zero hypothesis of survival
      rate <50% ), N= 23 patients

      Total length of the study 4 years Inclusion period time : 3 years Time of participation per
      patient : 1 year Number of center and/or participating departments: 24 Mean number of
      patients included per year and per center : 0 to 3 patients
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Endoscopic surgical treatment
primary purpose: Treatment
masking: None (Open Label)
measure: Local control rate and survival rate
time frame: 3 months
description: To evaluate the local control rate and survival rate at 3 months after radical endoscopic transnasal surgery extended towards the skull base in association with antifungal therapy and early surgical reevaluation of the extent of the disease.
measure: Survival rates
time frame: 6 and 12 months
description: Survival rates at 6 and 12 months
measure: Study of the response rate
time frame: 1 and 3 months
description: Study of the response rate at 1 and 3 months according to Segar criteria (Segal, Clin Infect Dis) using clinical, mycological and radiological evaluation.
measure: Study of the local control
time frame: 3 months
description: Study of the local control obtained at day 7+/-5 days and survival rate and response rate at 3 months.
measure: Study of the association between local control and survival rate and response rate
time frame: 3 months
description: Study of the association between local control obtained at 1 month and survival rate and response rate at 3 months.
measure: Evaluation of the interest of CT PET scan
time frame: 3 months
description: Evaluation of the interest of CT PET scan in studying clinical response at 3 months.
measure: Radiological staging
time frame: 3 months
description: Radiological staging: comparison of the initial extent of the mucormycosis at day 0 by CT scan and MRI and survival rate at 3 months and local control obtained at day 7.
measure: Dosage of the amphotericin B concentration inside tissues
time frame: Day 7
description: Dosage of the amphotericin B concentration inside tissues (infeusingcted and at the border of infected tissues) as obtained with biopsies at day 7.
measure: Search for biofilms using confocal microscopy
time frame: Day 0 and Day 7
description: Search for biofilms using confocal microscopy on infected tissues biopsies
measure: Staging of sequellae
time frame: 3 months, 6 months and 1 year
description: Staging of sequellae using quality of life questionnaires
measure: Bank of mucormycosis tissues
time frame: Day 0, Day 7, Day 14, D21 and Day 28
description: Bank of mucormycosis tissues at -80°C
arm group label: Multiple Surgeries
arm group type: Experimental
description: Patients undergoing transnasal endoscopic surgery
intervention type: Procedure
intervention name: Multiple transnasal endoscopic surgeries
description: Transnasal endoscopic surgery extended to the skull base
arm group label: Multiple Surgeries
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Romain KANIA, PhD, MD
role: Principal Investigator
affiliation: Assistance Publique - Hôpitaux de Paris
facility: 
country: France
responsible party type: Sponsor
mesh term: Mucormycosis
mesh term: Zygomycosis