<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/NCT04424134</url>
  </required_header>
  <id_info>
    <org_study_id>MSU160520</org_study_id>
    <nct_id>NCT04424134</nct_id>
  </id_info>
  <brief_title>BromhexIne And Spironolactone For CoronаVirUs Infection Requiring HospiTalization</brief_title>
  <acronym>BISCUIT</acronym>
  <official_title>Open Label Randomized Clinical Trial BromhexIne And Spironolactone For CoronаVirUs Infection Requiring HospiTalization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lomonosov Moscow State University Medical Research and Educational Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lomonosov Moscow State University Medical Research and Educational Center</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>
      Patients with mild and severe COVID 19 will be randomized 1:1 into two groups: experimental,&#xD;
      which will get bromhexine and spironolactone, and control. Patients will get investigated&#xD;
      therapy for ten days. Change in clinical assessment score COVID 19 (CAS COVID 19) between&#xD;
      baseline and 12th day will be evaluated as a primary endpoint. Forty-five-day risk of death&#xD;
      or mechanical ventilation will also be assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 16, 2020</start_date>
  <completion_date type="Anticipated">August 23, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 18, 2020</primary_completion_date>
  <phase>Phase 3</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 (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in clinical assessment score COVID 19 (CAS COVID 19)</measure>
    <time_frame>baseline, day 12</time_frame>
    <description>change in CAS COVID 19 between baseline and 12th +/- 2 days&#xD;
CAS COVID 19 measures clinical and laboratory parameters in 7 domains:&#xD;
respiratory rate (&lt; 18 - 0 point; 18-22 - 1 point; 23-26 - 2 point; &gt;26 - 3 point) body temperature (35.5 - 37.0 - 0 point; &lt; 35.5 - 1 point; 37.1 - 38.5 - 1 point; &gt; 38.5 - 2 point) Sp02 without support oxygen (&gt; 93% - 0 point; 90-93% - 1 point; &lt; 90% - 2 point) ventilation (not required - 0 point; low-flow ventilation - 1 point; Non-invasive positive pressure ventilation - 2 point; mechanical ventilation - 3 point) C-reactive protein (&gt; 10 - 0 point; 10-59 - 1 point; 60-120 - 2 point; &gt; 120 - 3 point) d - dimer (&lt; 0.51 - 0 point; 0.51 - 2.0 - 1 point; 2.01 - 5.0 - 2, &gt; 5.0 - 3 point) exposure area on lung CT (no pneumonia - 0; 1-24% - 1 point; 25-50% - 2; 51-75% - 3, &gt; 75% - 4).&#xD;
Minimal number of points - 0; max - 20.Lower the score-better health</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>- Combine endpoint -</measure>
    <time_frame>12 days, 45 days</time_frame>
    <description>time to death or mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive protein</measure>
    <time_frame>12 days, 45 days</time_frame>
    <description>- Change from baseline in C-reactive protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-dimer</measure>
    <time_frame>12 days, 45 days</time_frame>
    <description>- Change from baseline in D-dimer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol Group. EQ-5D™</measure>
    <time_frame>12 days, 45 days</time_frame>
    <description>Change from baseline in EQ-5D.&#xD;
The EQ-5D descriptive system comprises the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box to the most appropriate statement. This decision results into a 1-digit number, . The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EuroQol Group. EQ VAS</measure>
    <time_frame>12 days, 45 days</time_frame>
    <description>Change from baseline in EQ VAS&#xD;
EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome by patient's own judgement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HADS</measure>
    <time_frame>14 days, 45 days</time_frame>
    <description>- Change from baseline Hospital Anxiety and Depression Scale/The Hospital Anxiety and Depression Scale (HADS) is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. Items are rated on a 4-point severity scale. The HADS produces two scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states. Scores of greater than or equal to 11 on either scale indicate a definitive case</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>up to 45 days</time_frame>
    <description>Time from admission to the hospital to discharge form the hospital</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>Bromhexine And Spironolactone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Base therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bromhexine and Spironolactone</intervention_name>
    <description>Bromhexine 8 mg x 4 times a day x 10 days Spironolactone 50 mg x once a day x 10 days</description>
    <arm_group_label>Bromhexine And Spironolactone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Base therapy</intervention_name>
    <description>Therapy currently recommended by Ministry of Health of Russian Federation for COVID 19 treatment</description>
    <arm_group_label>Base therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        signed inform consent COVID 19 with the mild and severe course. The diagnosis could be made&#xD;
        with positive polymerase chain reaction (PCR) (International Statistical Classification&#xD;
        (ICD-10) code - U07.1) and/or virus pneumonia in computer tomography (ICD 10 code - U07.2)&#xD;
        5. Lung exposure on CT more than 25% 6. Sp02 without supportive oxygen ≤ 93% 7. C-reactive&#xD;
        protein &gt; 60 mg/l or elevation of C reactive protein 3 times in 8-14 days after first&#xD;
        symptoms&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy and breastfeeding&#xD;
&#xD;
          -  hypersensitivity to Spironolactone&#xD;
&#xD;
          -  hypersensitivity to Bromhexine&#xD;
&#xD;
          -  Known liver failure&#xD;
&#xD;
          -  Glomerular filtration rate &lt;20 ml/ min&#xD;
&#xD;
          -  physician judgment that the patient will need mechanical ventilation in 24 hours&#xD;
&#xD;
          -  other indications for Spironolactone&#xD;
&#xD;
          -  Active cancer&#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_contact>
    <last_name>Julia Begrambekova</last_name>
    <phone>+79854679273</phone>
    <email>julia.begrambekova@ossn.ru</email>
  </overall_contact>
  <location>
    <facility>
      <name>Lomonosov Moscow State University Medical Research and Educational Center</name>
      <address>
        <city>Moscow</city>
        <state>Moscow Region</state>
        <zip>119620</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Julia Begrambekova, Phd</last_name>
      <phone>+79854679273</phone>
      <email>begrambekova@ossn.ru</email>
    </contact>
    <contact_backup>
      <last_name>Yana Orlova, Professor</last_name>
      <phone>+791651663002</phone>
      <email>yaorlova@mc.msu.ru</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 7, 2020</last_update_submitted>
  <last_update_submitted_qc>June 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID 19</keyword>
  <keyword>bromhexine</keyword>
  <keyword>spironolactone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spironolactone</mesh_term>
    <mesh_term>Bromhexine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>After publishing</ipd_time_frame>
    <ipd_access_criteria>any application for access the data will be evaluated by ethical commite of LOMONOSOV MOSCOW STATE UNIVERSITY MEDICAL RESEARCH AND EDUCATIONAL CENTER</ipd_access_criteria>
  </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/NCT04424134
org study id: MSU160520
nct id: NCT04424134
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients with mild and severe COVID 19 will be randomized 1:1 into two groups: experimental,
      which will get bromhexine and spironolactone, and control. Patients will get investigated
      therapy for ten days. Change in clinical assessment score COVID 19 (CAS COVID 19) between
      baseline and 12th day will be evaluated as a primary endpoint. Forty-five-day risk of death
      or mechanical ventilation will also be assessed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change from baseline in clinical assessment score COVID 19 (CAS COVID 19)
time frame: baseline, day 12
description: change in CAS COVID 19 between baseline and 12th +/- 2 days
CAS COVID 19 measures clinical and laboratory parameters in 7 domains:
respiratory rate (< 18 - 0 point; 18-22 - 1 point; 23-26 - 2 point; >26 - 3 point) body temperature (35.5 - 37.0 - 0 point; < 35.5 - 1 point; 37.1 - 38.5 - 1 point; > 38.5 - 2 point) Sp02 without support oxygen (> 93% - 0 point; 90-93% - 1 point; < 90% - 2 point) ventilation (not required - 0 point; low-flow ventilation - 1 point; Non-invasive positive pressure ventilation - 2 point; mechanical ventilation - 3 point) C-reactive protein (> 10 - 0 point; 10-59 - 1 point; 60-120 - 2 point; > 120 - 3 point) d - dimer (< 0.51 - 0 point; 0.51 - 2.0 - 1 point; 2.01 - 5.0 - 2, > 5.0 - 3 point) exposure area on lung CT (no pneumonia - 0; 1-24% - 1 point; 25-50% - 2; 51-75% - 3, > 75% - 4).
Minimal number of points - 0; max - 20.Lower the score-better health
measure: - Combine endpoint -
time frame: 12 days, 45 days
description: time to death or mechanical ventilation
measure: C-reactive protein
time frame: 12 days, 45 days
description: - Change from baseline in C-reactive protein
measure: D-dimer
time frame: 12 days, 45 days
description: - Change from baseline in D-dimer
measure: EuroQol Group. EQ-5D™
time frame: 12 days, 45 days
description: Change from baseline in EQ-5D.
The EQ-5D descriptive system comprises the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box to the most appropriate statement. This decision results into a 1-digit number, . The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
measure: EuroQol Group. EQ VAS
time frame: 12 days, 45 days
description: Change from baseline in EQ VAS
EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome by patient's own judgement.
measure: HADS
time frame: 14 days, 45 days
description: - Change from baseline Hospital Anxiety and Depression Scale/The Hospital Anxiety and Depression Scale (HADS) is a 14-item measure designed to assess anxiety and depression symptoms in medical patients, with emphasis on reducing the impact of physical illness on the total score. Items are rated on a 4-point severity scale. The HADS produces two scales, one for anxiety (HADS-A) and one for depression (HADS-D), differentiating the two states. Scores of greater than or equal to 11 on either scale indicate a definitive case
measure: Hospital length of stay
time frame: up to 45 days
description: Time from admission to the hospital to discharge form the hospital
arm group label: Bromhexine And Spironolactone
arm group type: Experimental
arm group label: Base therapy
arm group type: Active Comparator
intervention type: Drug
intervention name: Bromhexine and Spironolactone
description: Bromhexine 8 mg x 4 times a day x 10 days Spironolactone 50 mg x once a day x 10 days
arm group label: Bromhexine And Spironolactone
intervention type: Drug
intervention name: Base therapy
description: Therapy currently recommended by Ministry of Health of Russian Federation for COVID 19 treatment
arm group label: Base therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Julia Begrambekova
phone: +79854679273
email: julia.begrambekova@ossn.ru
facility: 
status: Recruiting
contact: 
contact backup: 
country: Russian Federation
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Spironolactone
mesh term: Bromhexine
sharing ipd: Yes
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: After publishing
ipd access criteria: any application for access the data will be evaluated by ethical commite of LOMONOSOV MOSCOW STATE UNIVERSITY MEDICAL RESEARCH AND EDUCATIONAL CENTER