<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/NCT04492358</url>
  </required_header>
  <id_info>
    <org_study_id>2020-002462-14</org_study_id>
    <nct_id>NCT04492358</nct_id>
  </id_info>
  <brief_title>Treatment for Moderate/Severe COVID-19 in a Fragile and Vulnerable Population, Admitted to a Geriatric Hospital Unit or in a Transicional Care Center</brief_title>
  <official_title>Phase 2/3, Randomized, Open Study to Compare the Efficacy and Safety of Colchicine and Glucocorticoids Compared With the Standard of Treatment for Moderate/Severe COVID-19 in a Fragile and Vulnerable Population, Admitted to a Geriatric Hospital Unit or in a Transicional Care Center</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maria Joyera Rodríguez</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacion Clinic per a la Recerca Biomédica</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Study to compare the efficacy and safety of colchicine and glucocorticoids compared with the&#xD;
      standard of treatment for moderate/severe COVID-19 in a fragile and vulnerable population,&#xD;
      admitted to a geriatric hospital unit or in a transicional care center&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    No candidates for the recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">October 22, 2020</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 31, 2021</primary_completion_date>
  <phase>Phase 2/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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients that a short cycle of steroids administered together with colchicine reduces mortality from COVID-19</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients that a short cycle of steroids (with prednisone 60 mg/d, in a single dose, for 3 consecutive days) administered together with colchicine (at doses of 0.5 to 1.5 mg/d, adjusted for weight and renal function, for 3 days and maintenance of 0.5 mg/d for 14 days in total) reduces mortality from COVID-19 in this population by at least 20%, compared to the approved standard treatment at participating centers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number and grade of adverse events at group of colchicine and glucocorticoids throughout the treatment and in the two weeks following treatment</measure>
    <time_frame>28 days</time_frame>
    <description>Number and grade of adverse events at group of colchicine and glucocorticoids throughout the treatment and in the two weeks following treatment according to the incidence of:&#xD;
mild adverse event&#xD;
serious adverse events&#xD;
hypersensitivity (allergic) reactions of grade &gt;=2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of patients who stop medication due to adverse events.</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of patients who stop medication due to adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of symptoms by COVID-19 in the two treatment arms</measure>
    <time_frame>28 days</time_frame>
    <description>Severity of symptoms by COVID-19 in the two treatment arms (response to treatment to be assessed by overall survival at 28 days from the start of treatment).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>colchicine + prednisone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prednisone should be administered for 3 consecutive days (60 mg/d) together with colchicine (at doses of 0.5 to 1.5 mg/d, adjusted for weight and renal function) for 3 days and maintained for 14 days in total (0.5 mg/d).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The standard treatment used in each site will be administered to the patients assigned to the control group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Colchicine</intervention_name>
    <description>Colchicine: ideal dose of 0.3 mg/kg/day (or the dose that approximates that adjusted for age, weight and kidney function, and 0.5 mg and 1 mg tablets)</description>
    <arm_group_label>colchicine + prednisone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone tablet</intervention_name>
    <description>Prednisone 60 mg/day, in a single dose, during 3 days</description>
    <arm_group_label>colchicine + prednisone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>standard of care</intervention_name>
    <description>The standard treatment used in each site will be administered to the patients assigned to the control group.</description>
    <arm_group_label>Standard treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Be at least 65 years old and be admitted to the Geriatrics Unit of the Internal&#xD;
             Medicine Service (Hospital Clínic de Barcelona) or to a transicional care center&#xD;
&#xD;
          2. Clinical diagnosis compatible with COVID-19 (in a favourable epidemiological context),&#xD;
             with a disease considered moderate (grade 3-4) or severe (grade 5) according to the&#xD;
             WHO 8-point ordinal scale for assessing clinical severity&#xD;
             (https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis). This&#xD;
             same scale will also be used to evaluate the evolution after the application of the&#xD;
             corresponding treatment. Baseline clinical parameters will include the presentation of&#xD;
             fever and any respiratory symptoms, both of upper respiratory tract and dyspnea,&#xD;
             affecting the general state or gastrointestinal manifestations, since it is known that&#xD;
             in elderly people the COVID-19 can present with atypical symptoms for a time that is&#xD;
             difficult to determine, but it also tends to evolve to respiratory failure quickly and&#xD;
             is associated with high mortality. For this reason, regardless of the time that has&#xD;
             elapsed since the estimated onset of symptoms, patients with moderate - WHO grade 3,&#xD;
             in whom the presence of fever, mild dyspnea or any gastrointestinal manifestation&#xD;
             attributable to COVID-19 make an admission (in the case of hospital) and directed&#xD;
             treatment (in all cases) advisable, will be candidates for inclusion in the study.&#xD;
             Patients with moderate disease and oxygen requirements (WHO grade 4) and patients with&#xD;
             severe pneumonia, but who can be managed initially with high flow oxygen therapy (WHO&#xD;
             grade 5) may also be included in the study. The clinical diagnosis may be supported by&#xD;
             radiological changes (via chest radiography, if available) suggestive of bilateral&#xD;
             (established or incipient) pneumonia. At the time of diagnosis, biomarkers will also&#xD;
             be collected, in an analysis that will include increased levels of C-reactive protein&#xD;
             [PCR] and/or ferritin and microbiological confirmation of SARS-CoV-2.&#xD;
&#xD;
          3. Patients in whom the current clinical situation and the basal functional situation&#xD;
             condition a prognosis that makes them consider a limited therapeutic ceiling, which&#xD;
             includes the contraindication of applying more aggressive (e.g. non-invasive&#xD;
             ventilation) or invasive measures (e.g. cardiopulmonary resuscitation or orotracheal&#xD;
             intubation and mechanical ventilation), both in patients admitted to the Geriatric&#xD;
             Unit (Hospital Clínic de Barcelona) and in those admitted to a transicional care&#xD;
             center. The latter patients are also not considered for transfer to a third level&#xD;
             hospital (according to the criteria of fragility, available on page 14 of the CatSalut&#xD;
             action protocols&#xD;
             (https://canalsalut.gencat.cat/web/.content/_A-Z/C/coronavirus-2019-ncov/material-divu&#xD;
             lgatiu/recull-protocol-pneumonia.pdf).&#xD;
&#xD;
          4. Patient with a general condition that allows him/her to take the medication orally,&#xD;
             without risk of bronchial aspiration.&#xD;
&#xD;
          5. Acceptance by the patient or responsible family member to participate in the study&#xD;
             (written consent).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The clinical situation of an advanced or terminal illness, according to the clinical&#xD;
             judgment of the doctor in charge and as defined by the Spanish Society for Palliative&#xD;
             Care (SECPAL), which describes it as an advanced illness in an evolutionary and&#xD;
             irreversible phase with multiple symptoms, emotional impact, loss of autonomy, with&#xD;
             very little or no capacity to respond to specific treatment and with a life expectancy&#xD;
             limited to weeks or months, in a context of progressive fragility&#xD;
             (http://envejecimiento.csic.es/documentos/documentos/navarro-cuidadospaliativos-01.pdf&#xD;
             ).&#xD;
&#xD;
          2. Clinical status which is advanced and severe or in which the level of consciousness&#xD;
             has deteriorated and the oral route of taking the medication is not safely tolerated&#xD;
             (in the opinion of the doctor in charge)&#xD;
&#xD;
          3. Taking any of the drugs in the trial (colchicine or prednisone) chronically or&#xD;
             intermittently in the 7 days prior to study inclusion.&#xD;
&#xD;
          4. Absolute contraindication to the use of the study medication, including&#xD;
             hypersensitivity to the active substance or to any of its excipients, severe renal&#xD;
             failure (glomerular filtration [GF] creatinine clearance or Clcr &lt;30 ml/min) and&#xD;
             patients undergoing haemodialysis, severe liver failure, severe gastrointestinal&#xD;
             disorders, gastric ulcer or blood dyscrasias.&#xD;
&#xD;
          5. Concomitant treatment with macrolides (clarithromycin, erythromycin, telithromycin),&#xD;
             antifungals (itraconazole, ketoconazole), cyclosporine and antivirals&#xD;
             (lopinavir/ritonavir, indinavir, nelfinavir, saquinavir), all potent inhibitors of&#xD;
             CYP3A4 (key cytochrome in the colchicine metabolism pathway).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Centre Blauclínic Dolors Aleu</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic, Department of Internal Medicine</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Sant Antoni</name>
      <address>
        <city>Barcelona</city>
        <zip>08038</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 28, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 30, 2020</study_first_posted>
  <last_update_submitted>February 17, 2023</last_update_submitted>
  <last_update_submitted_qc>February 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Fundacion Clinic per a la Recerca Biomédica</investigator_affiliation>
    <investigator_full_name>Maria Joyera Rodríguez</investigator_full_name>
    <investigator_title>Clinical Research Manager</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Colchicine</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/NCT04492358
org study id: 2020-002462-14
nct id: NCT04492358
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Study to compare the efficacy and safety of colchicine and glucocorticoids compared with the
      standard of treatment for moderate/severe COVID-19 in a fragile and vulnerable population,
      admitted to a geriatric hospital unit or in a transicional care center
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients that a short cycle of steroids administered together with colchicine reduces mortality from COVID-19
time frame: 28 days
description: Number of patients that a short cycle of steroids (with prednisone 60 mg/d, in a single dose, for 3 consecutive days) administered together with colchicine (at doses of 0.5 to 1.5 mg/d, adjusted for weight and renal function, for 3 days and maintenance of 0.5 mg/d for 14 days in total) reduces mortality from COVID-19 in this population by at least 20%, compared to the approved standard treatment at participating centers.
measure: Number and grade of adverse events at group of colchicine and glucocorticoids throughout the treatment and in the two weeks following treatment
time frame: 28 days
description: Number and grade of adverse events at group of colchicine and glucocorticoids throughout the treatment and in the two weeks following treatment according to the incidence of:
mild adverse event
serious adverse events
hypersensitivity (allergic) reactions of grade >=2
measure: Percentage of patients who stop medication due to adverse events.
time frame: 28 days
description: Percentage of patients who stop medication due to adverse events.
measure: Severity of symptoms by COVID-19 in the two treatment arms
time frame: 28 days
description: Severity of symptoms by COVID-19 in the two treatment arms (response to treatment to be assessed by overall survival at 28 days from the start of treatment).
arm group label: colchicine + prednisone
arm group type: Experimental
description: Prednisone should be administered for 3 consecutive days (60 mg/d) together with colchicine (at doses of 0.5 to 1.5 mg/d, adjusted for weight and renal function) for 3 days and maintained for 14 days in total (0.5 mg/d).
arm group label: Standard treatment
arm group type: Active Comparator
description: The standard treatment used in each site will be administered to the patients assigned to the control group.
intervention type: Drug
intervention name: Colchicine
description: Colchicine: ideal dose of 0.3 mg/kg/day (or the dose that approximates that adjusted for age, weight and kidney function, and 0.5 mg and 1 mg tablets)
arm group label: colchicine + prednisone
intervention type: Drug
intervention name: Prednisone tablet
description: Prednisone 60 mg/day, in a single dose, during 3 days
arm group label: colchicine + prednisone
intervention type: Drug
intervention name: standard of care
description: The standard treatment used in each site will be administered to the patients assigned to the control group.
arm group label: Standard treatment
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: Spain
responsible party type: Sponsor-Investigator
investigator affiliation: Fundacion Clinic per a la Recerca Biomédica
investigator full name: Maria Joyera Rodríguez
investigator title: Clinical Research Manager
mesh term: COVID-19
mesh term: Prednisone
mesh term: Colchicine