<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/NCT04483635</url>
  </required_header>
  <id_info>
    <org_study_id>MP-21-2021-3044</org_study_id>
    <nct_id>NCT04483635</nct_id>
  </id_info>
  <brief_title>PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams</brief_title>
  <acronym>PROTECT</acronym>
  <official_title>PROTECT RCT (PRevention of COVID-19 With Oral Vitamin D Supplemental Therapy in Essential healthCare Teams</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. Justine's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Laboratoire RIVA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. Justine's Hospital</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>
      In this 16-week randomized control study, health care workers will receive a bolus dose&#xD;
      followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will&#xD;
      test whether high-dose of vitamin D supplementation decreases the incidence of&#xD;
      laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration,&#xD;
      as well as work absenteeism among health care workers (HCW) in setting at high-risk of&#xD;
      contact with COVID-19 cases in high COVID-19 incidence areas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Design. A 16-week triple-blind, placebo-controlled parallel-group, randomised trial of&#xD;
      high-dose vitamin D supplementation compared to placebo in health care workers (HCW).&#xD;
&#xD;
      Subjects: HCW caring for individuals at high-risk of infection (i.e., COVID-suspected or&#xD;
      confirmed cases) will be randomly allocated in a 1:1 ratio in variable block size to:&#xD;
      Intervention-1 oral loading dose of 100,000 IU vitamin D3 + 10000 IU weekly vitamin D3 or&#xD;
      Control-identical placebo loading dose + daily placebo. Follow-up: 2 (randomisation and&#xD;
      end-of-study) virtual or in-person visits with weekly reminders, brief health and work-status&#xD;
      questionnaire.&#xD;
&#xD;
      Randomisation/allocation concealment: Randomisation will be implemented using a&#xD;
      computer-generated random list stratified by regions; health care workers will be allocated&#xD;
      (1:1) using permuted block randomisation to enhance concealment.&#xD;
&#xD;
      Sample size: A total of 2414 healthcare workers will provide 80% power to detect a 20%&#xD;
      reduction in the risk of laboratory-confirmed COVID-19 infection. Given uncertainties in the&#xD;
      infection progression, a Bayesian adaptive design is used where the posterior probability of&#xD;
      effectiveness is the basis of inference and decision making, for study continuation or&#xD;
      termination.&#xD;
&#xD;
      Procedures. Use of remote or in-person randomisation and/or end-of-study visits and remote&#xD;
      documentation of outcomes via electronic communication, mailing of biological samples, and&#xD;
      external databases will facilitate enrolment, monitoring, and retention of motivated HCW in&#xD;
      this high-intensity trial.&#xD;
&#xD;
      Data analyses: An intention-to-treat analysis will be carried out on all randomized&#xD;
      participants. Efficacy and safety analyses will be performed under allocation concealment&#xD;
      with unblinding occurring after trial completion and analysis of primary outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    A premature discontinuation was recommended by the Data Safety Monitoring Board and agreed upon&#xD;
    by the principal investigator, because the significantly lower recruitment than planned, in the&#xD;
    context of mass vaccination of the target population.&#xD;
  </why_stopped>
  <start_date type="Actual">February 8, 2021</start_date>
  <completion_date type="Actual">May 25, 2021</completion_date>
  <primary_completion_date type="Actual">May 4, 2021</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>
    <intervention_model_description>Parallel-group, placebo controlled trial of vitamin D3 supplementation</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>The Laboratoires Riva will provide the active vitamin D3 and placebo pills, identical in appearance, which will be pre-packaged in coded 60-pill bottles. A web-based randomisation system will allow the research personnel (RP) to log in, obtain a randomization number, and dispense study drugs, pre-prepared by the Central pharmacy, in masked kits.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in incidence of laboratory-confirmed COVID-19 infection</measure>
    <time_frame>16 weeks</time_frame>
    <description>documented by salivary or NP samples obtained clinically for screening or diagnostic purposes throughout the study period, self-obtained salivary samples at endpoint, analysed by RT-qPCR or COVID-19 seroconversion at endpoints</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Distribution of disease severity</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of symptoms in COVID-19 positive participants</measure>
    <time_frame>up to 16 weeks</time_frame>
    <description>For asymptomatic positive COVID-19 participants, symptoms will be recorded in a daily diary up to 14 days. Symptomatic positive COVID-19 participants will record their symptoms in a daily diary up to 48 hours after the resolution of symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with COVID-19 positive IgG serology</measure>
    <time_frame>16 weeks</time_frame>
    <description>SARS-CoV-2 IgG Diasorin on Liaison XL platform</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of workday absences due to COVID-19 suspected/confirmed infection</measure>
    <time_frame>16 weeks</time_frame>
    <description>Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of workday absences for any reason</measure>
    <time_frame>16 weeks</time_frame>
    <description>Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse health events</measure>
    <time_frame>16 weeks</time_frame>
    <description>Number and distribution of adverse health events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>10 placebo tablets taken orally at baseline, followed by 1 placebo tablet once a week for 16 weeks&#xD;
Note that the study may be prolonged according to the overall infection rate monitored monthly.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin D3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 tablets containing 10,000 IU (total : 100,000 IU) of Vitamin D3 taken orally at baseline, followed by 10,000 IU once a week for 16 weeks.&#xD;
Note that the study may be prolonged according to the overall infection rate monitored monthly.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Weekly oral dose of placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin D</intervention_name>
    <description>Weekly oral dose of Vitamin D</description>
    <arm_group_label>Vitamin D3</arm_group_label>
    <other_name>cholecalciferol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  are aged ≥18 and &lt;70 years old;&#xD;
&#xD;
          -  licenced to practice in Quebec;&#xD;
&#xD;
          -  working or scheduled to work over the next 16 weeks in a setting at high-risk of&#xD;
             contact with COVID-19 infected individuals, particularly (but not only) those involved&#xD;
             with aerosol generating medical procedures in hospitals and/or caring for patients in&#xD;
             long-term care facilities;&#xD;
&#xD;
          -  working in high COVID incidence areas;&#xD;
&#xD;
          -  covered by the RAMQ for medical services and hospitalisations;&#xD;
&#xD;
          -  has a personal email or phone (to which to send every two weeks a reminder and&#xD;
             questionnaire by email or text messages);&#xD;
&#xD;
          -  has a fixed address (to which to send the material) in the greater Montreal or&#xD;
             surrounding areas.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  vitamin D supplementation &gt;400 IU/day or &gt;12,000 IU/month in past 3 months;&#xD;
&#xD;
          -  intention to take &gt;400 IU per day during the study period;&#xD;
&#xD;
          -  suspected or previously documented COVID-19 infection;&#xD;
&#xD;
          -  history of nephrolithiasis, hypercalcemia, hyperphosphatemia, hyperparathyroidism,&#xD;
             granulomatosis disease (e.g., tuberculosis, sarcoidosis), renal impairment/failure, or&#xD;
             active cancer;&#xD;
&#xD;
          -  use of any of the following medications: lithium, teriparatide, or digoxin;&#xD;
&#xD;
          -  anticipated prolonged absence from work during the study period (i.e., pregnancy);&#xD;
&#xD;
          -  enrolment in a concurrent randomized trial;&#xD;
&#xD;
          -  has received a vaccine against COVID-19.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>69 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Francine M Ducharme, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. Justine's Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Cecile Tremblay, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHUM</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHUM</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2W 1T8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Sainte-Justine (CHUSJ)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>May 26, 2021</last_update_submitted>
  <last_update_submitted_qc>May 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. Justine's Hospital</investigator_affiliation>
    <investigator_full_name>Professor Francine Ducharme</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Vitamin D</keyword>
  <keyword>Primary prevention</keyword>
  <keyword>Health care workers</keyword>
  <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>Vitamin D</mesh_term>
    <mesh_term>Cholecalciferol</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/NCT04483635
org study id: MP-21-2021-3044
nct id: NCT04483635
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this 16-week randomized control study, health care workers will receive a bolus dose
      followed by a weekly dose of vitamin D or a placebo bolus and weekly dose. This study will
      test whether high-dose of vitamin D supplementation decreases the incidence of
      laboratory-confirmed COVID19 infection (primary outcome), reduces illness severity, duration,
      as well as work absenteeism among health care workers (HCW) in setting at high-risk of
      contact with COVID-19 cases in high COVID-19 incidence areas.
Design. A 16-week triple-blind, placebo-controlled parallel-group, randomised trial of
      high-dose vitamin D supplementation compared to placebo in health care workers (HCW).

      Subjects: HCW caring for individuals at high-risk of infection (i.e., COVID-suspected or
      confirmed cases) will be randomly allocated in a 1:1 ratio in variable block size to:
      Intervention-1 oral loading dose of 100,000 IU vitamin D3 + 10000 IU weekly vitamin D3 or
      Control-identical placebo loading dose + daily placebo. Follow-up: 2 (randomisation and
      end-of-study) virtual or in-person visits with weekly reminders, brief health and work-status
      questionnaire.

      Randomisation/allocation concealment: Randomisation will be implemented using a
      computer-generated random list stratified by regions; health care workers will be allocated
      (1:1) using permuted block randomisation to enhance concealment.

      Sample size: A total of 2414 healthcare workers will provide 80% power to detect a 20%
      reduction in the risk of laboratory-confirmed COVID-19 infection. Given uncertainties in the
      infection progression, a Bayesian adaptive design is used where the posterior probability of
      effectiveness is the basis of inference and decision making, for study continuation or
      termination.

      Procedures. Use of remote or in-person randomisation and/or end-of-study visits and remote
      documentation of outcomes via electronic communication, mailing of biological samples, and
      external databases will facilitate enrolment, monitoring, and retention of motivated HCW in
      this high-intensity trial.

      Data analyses: An intention-to-treat analysis will be carried out on all randomized
      participants. Efficacy and safety analyses will be performed under allocation concealment
      with unblinding occurring after trial completion and analysis of primary outcomes.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel-group, placebo controlled trial of vitamin D3 supplementation
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: The Laboratoires Riva will provide the active vitamin D3 and placebo pills, identical in appearance, which will be pre-packaged in coded 60-pill bottles. A web-based randomisation system will allow the research personnel (RP) to log in, obtain a randomization number, and dispense study drugs, pre-prepared by the Central pharmacy, in masked kits.
measure: Change in incidence of laboratory-confirmed COVID-19 infection
time frame: 16 weeks
description: documented by salivary or NP samples obtained clinically for screening or diagnostic purposes throughout the study period, self-obtained salivary samples at endpoint, analysed by RT-qPCR or COVID-19 seroconversion at endpoints
measure: Distribution of disease severity
time frame: up to 16 weeks
description: 5-category ordinal variable [asymptomatic, mild (managed at home); moderate (hospitalisation without supplemental oxygen; severe (oxygen supplementation); critical (mechanical ventilation/death)
measure: Duration of symptoms in COVID-19 positive participants
time frame: up to 16 weeks
description: For asymptomatic positive COVID-19 participants, symptoms will be recorded in a daily diary up to 14 days. Symptomatic positive COVID-19 participants will record their symptoms in a daily diary up to 48 hours after the resolution of symptoms
measure: Number of participants with COVID-19 positive IgG serology
time frame: 16 weeks
description: SARS-CoV-2 IgG Diasorin on Liaison XL platform
measure: Number of workday absences due to COVID-19 suspected/confirmed infection
time frame: 16 weeks
description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases
measure: Number of workday absences for any reason
time frame: 16 weeks
description: Participant-reported; reported by Direction of Human Resource (or for physicians, Direction des services professionnelles) databases
measure: Adverse health events
time frame: 16 weeks
description: Number and distribution of adverse health events
arm group label: Placebo
arm group type: Placebo Comparator
description: 10 placebo tablets taken orally at baseline, followed by 1 placebo tablet once a week for 16 weeks
Note that the study may be prolonged according to the overall infection rate monitored monthly.
arm group label: Vitamin D3
arm group type: Experimental
description: 10 tablets containing 10,000 IU (total : 100,000 IU) of Vitamin D3 taken orally at baseline, followed by 10,000 IU once a week for 16 weeks.
Note that the study may be prolonged according to the overall infection rate monitored monthly.
intervention type: Dietary Supplement
intervention name: Placebo
description: Weekly oral dose of placebo
arm group label: Placebo
intervention type: Dietary Supplement
intervention name: Vitamin D
description: Weekly oral dose of Vitamin D
arm group label: Vitamin D3
other name: cholecalciferol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 69 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Francine M Ducharme, MD
role: Principal Investigator
affiliation: St. Justine's Hospital
last name: Cecile Tremblay, MD
role: Principal Investigator
affiliation: CHUM
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: St. Justine's Hospital
investigator full name: Professor Francine Ducharme
investigator title: Principal Investigator
mesh term: COVID-19
mesh term: Vitamin D
mesh term: Cholecalciferol