<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/NCT04446104</url>
  </required_header>
  <id_info>
    <org_study_id>2020/00561</org_study_id>
    <nct_id>NCT04446104</nct_id>
  </id_info>
  <brief_title>A Preventive Treatment for Migrant Workers at High-risk of COVID-19</brief_title>
  <official_title>A Randomized Open-label Prophylaxis Trial Among Migrant Workers at High-risk of COVID-19 (DORM Trial)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National University Hospital, Singapore</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In December 2019, a novel coronavirus, now called COVID-19, emerged as a global health threat&#xD;
      from Wuhan, China. Within weeks, the contagious virus spread within and between communities,&#xD;
      causing a lower respiratory tract infection dominated by symptoms of fever, cough and sore&#xD;
      throat. The incubation period was estimated at between 5 to 7 days, but could last as long as&#xD;
      14 days. Although COVID-19 causes a mostly mild and self-limiting disease, respiratory&#xD;
      involvement has been reported in about 5% of the population, requiring supplemental oxygen&#xD;
      and even ventilatory support to relieve hypoxia. Alveolar damage, fibrosis and consolidation&#xD;
      have been reported in radiologic and post-mortem studies. Existing data suggest a mortality&#xD;
      rate of COVID-19 is approximately 1-2%, higher among individuals with pre-existing&#xD;
      comorbidities and in healthcare systems with suboptimal access to ventilatory support.&#xD;
&#xD;
      Given its high transmissibility, COVID-19 has quickly spread across the globe within a short&#xD;
      interval. By 27 April 2020, over 3 million people around the world have been diagnosed with&#xD;
      COVID-19, and more 200,000 have succumbed to the disease. As a proportion of patients&#xD;
      manifest mild or no symptoms, these numbers are likely an underestimate of the actual number&#xD;
      of patients with COVID-19. More disconcertingly, patients are known to shed viruses despite&#xD;
      mild or no symptoms, making it essential that a collective approach against COVID-19&#xD;
      incorporate active pharmacological treatment to prevent or mitigate virus pathogenesis prior&#xD;
      to its potential evolution to cause respiratory distress. To date, clinical trials have&#xD;
      focused on the treatment of hospitalised patients diagnosed with COVID-19; only few have&#xD;
      examined the clinical benefits of pharmacological agents despite few compelling in vitro&#xD;
      data.&#xD;
&#xD;
      The relatively high transmission of COVID-19 in a closed dormitory environment of migrant&#xD;
      workers in Singapore presents a real-life scenario where a prophylaxis treatment could reduce&#xD;
      the impact of the disease. In Singapore, there are well grounded concerns an excess in cases&#xD;
      could pose the possibility of strain in healthcare system and mentally drain her workers. The&#xD;
      availability of an effective prophylaxis treatment is highly desirable to potentially reduce&#xD;
      this burden. Data from the current study could also have implications on how future outbreaks&#xD;
      in high-density areas should be managed, especially when residents are subjected to&#xD;
      quarantine and isolation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a pragmatic, open-label, randomised study with 4 interventional and 1 control arms.&#xD;
      Individuals will be recruited from migrant worker dormitories, and written informed consent&#xD;
      taken prior to enrolment. Randomisation will be done by the level within the dormitory&#xD;
      building and predetermined each day according to a randomisation schema done by an&#xD;
      independent statistician. This will obviate the potential for bias due to drug exchange&#xD;
      between study individuals.&#xD;
&#xD;
      The 5 arms consist of:&#xD;
&#xD;
        -  Experimental arms&#xD;
&#xD;
             1. Hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days&#xD;
                (1,000 study subjects)&#xD;
&#xD;
             2. Ivermectin tablet 12mg single dose (1,000 study subjects)&#xD;
&#xD;
             3. Zinc tablet 80 mg/vitamin C 500mg daily for 42 days (1,000 study subjects)&#xD;
&#xD;
             4. Povidone-iodine throat spray (3 times daily) for 42 days (1,000 study subjects)&#xD;
&#xD;
        -  Control arm 5) Vitamin C tablet 500mg daily for 42 days (1,000 study subjects)&#xD;
&#xD;
      Study information sheet will be circulated in selected buildings within the dormitory 1-4&#xD;
      days before recruitment starts. All publicity materials and informed consent form will be&#xD;
      translated to the different languages (e.g. Tamil, Bengali, Chinese, Burmese and Malay). A&#xD;
      translator will be present to aid translation if necessary. Study subjects will be given&#xD;
      ample time to ask questions relating to the study. Prospective participants will respond by&#xD;
      showing up to recruitment stations at designated dates and times. Facilitators from the&#xD;
      dormitory will be engaged to assist with the ground crowd-control. Prospective videos will be&#xD;
      shown to inform the subject on the purpose, study inclusion and exclusion criteria, study&#xD;
      medications, blood taking, reporting of adverse effects and follow-up visits. Informed&#xD;
      consent will be taken before all study-related procedures are performed, including study&#xD;
      eligibility. Translators will also help translate the daily questionnaires.&#xD;
&#xD;
      During the baseline recruitment,&#xD;
&#xD;
        1. History of symptoms, comorbidities and prior illnesses will be asked. Specific questions&#xD;
           include presence or absence of the following symptoms: Fever, chills, myalgia, headache,&#xD;
           diarrhoea, running nose, anosmia, loss of taste, sore throat, dry cough, shortness of&#xD;
           breath.&#xD;
&#xD;
        2. Measurements of study subjects' parameters such as weight, height, temperature, pulse&#xD;
           rate and blood pressure will be recorded. Subjects randomised to Ivermectin arm and&#xD;
           subsequently found to weigh below 60 kg will be randomised to other treatment arms.&#xD;
           Subjects randomised to hydroxychloroquine arm and found to have systolic blood pressure&#xD;
           &gt;150 mmHg and/or diastolic blood pressure &gt;90 mmHg and/or heart rate &gt;100 beats per&#xD;
           minute will also be randomized to other treatment arms.&#xD;
&#xD;
        3. 12-lead electrocardiogram (ECG) will be performed in patients randomised to receive&#xD;
           hydroxychloroquine. Only those with corrected QT values less than 450 ms, no cardiac&#xD;
           arrhythmia and no ventricular hypertrophy will be allowed to receive hydroxychloroquine.&#xD;
           Those with corrected QT values more than 450 ms, cardiac arrhythmia and ventricular&#xD;
           hypertrophy will be randomised to other treatment arms.&#xD;
&#xD;
        4. Blood sample (20 mL) will be obtained to test Immunoglobulin G/M against SARS-CoV-2.&#xD;
           Depending on the findings, additional tests will be performed to explore potential&#xD;
           biological reasons underpinning these observations. The choice of markers may include&#xD;
           pathway-specific biomarkers targeting inflammation, oxidative stress, lipid parameters,&#xD;
           as well as organ-specific ones such as renal and liver parameters. Given the large&#xD;
           sample size and high costs of analysis, the study team will prioritise more detailed&#xD;
           investigations in a targeted group of patients depending on the final findings. None of&#xD;
           these blood results is a screening criteria for study participation. The investigator&#xD;
           will share abnormal to the study subjects abnormal results of their renal and liver&#xD;
           parameters should these tests are tested following study completion. The extent on&#xD;
           investigation, however, depends on funding support. In this study, renal and hepatic&#xD;
           dysfunction will be based on physician-diagnosed and self-declaration on the part of the&#xD;
           study subject. All clinical information will be verified by a senior physician on-site.&#xD;
&#xD;
        5. Study medications will be packed with clear instructions written on the packing bag. The&#xD;
           package will be distributed to each subject based on the randomised treatment assigned.&#xD;
&#xD;
        6. Study participants will be given a study card to remind them to submit their symptoms&#xD;
           daily and to record the times when they consume their medications. They will also be&#xD;
           asked to present this card to doctors at the medical post or hospital should they seek&#xD;
           medical assistance. In the events of acute respiratory infection and hospitalization,&#xD;
           lab testing will be done as clinically indicated. Subjects on ventilator support who are&#xD;
           not able to take oral medications may discontinue taking the study drug. However,&#xD;
           subjects will remain in the study for collection of data on duration of mechanical&#xD;
           ventilation for analysis.&#xD;
&#xD;
      During final study visit,&#xD;
&#xD;
        1. The study team, including investigators, will be present at the dormitory. A repeated&#xD;
           blood sample (20mL) will be collected for serological tests. Measurements of study&#xD;
           subjects' parameters such as weight (using Tanita BC-418 and Tanita BC-420MA for&#xD;
           bio-electrical impedance analysis), height, blood pressure will be taken. ECG will be&#xD;
           done only for subjects in hydroxychloroquine arm. History will be taken including&#xD;
           symptoms of fever, chills, myalgia, headache, diarrhoea, running nose, anosmia, loss of&#xD;
           taste, sore throat, dry cough, shortness of breath and the duration of such symptoms, if&#xD;
           any.&#xD;
&#xD;
        2. Balance medication and packaging retrieval to do medication accounting and checking for&#xD;
           adherence to assigned treatment arm&#xD;
&#xD;
        3. Discharged from study if no adverse events to follow-up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 13, 2020</start_date>
  <completion_date type="Actual">August 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 31, 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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Acute respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
    <description>Acute respiratory illness is defined by acute onset with any key respiratory symptoms including cough, shortness of breath, sore throat, runny nose and change in smell.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Febrile respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of hospitalization for COVID-19 and non-COVID-19 related indications in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events and serious adverse events in control arm (Vitamin C)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Drug discontinuation due to adverse events in control arm (Vitamin C)</measure>
    <time_frame>At the end of study dosing, which is day 42</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">4257</enrollment>
  <condition>Covid-19</condition>
  <arm_group>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ivermectin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive ivermectin tablet 12mg single dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Zinc/ Vitamin C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive zinc tablet 80 mg/vitamin C 500mg daily for 42 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Povidone-iodine throat spray</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive povidone-iodine throat spray (3 times daily) for 42 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive vitamin C tablet 500mg daily for 42 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydroxychloroquine Sulfate Tablets</intervention_name>
    <description>Hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days</description>
    <arm_group_label>Hydroxychloroquine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ivermectin 3mg Tab</intervention_name>
    <description>Ivermectin tablet 12mg single dose</description>
    <arm_group_label>Ivermectin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zinc</intervention_name>
    <description>Zinc tablet 80 mg/vitamin C 500mg daily for 42 days</description>
    <arm_group_label>Zinc/ Vitamin C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Povidone-Iodine</intervention_name>
    <description>Povidone-iodine throat spray (3 times daily) for 42 days</description>
    <arm_group_label>Povidone-iodine throat spray</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>Vitamin C tablet 500mg daily for 42 days</description>
    <arm_group_label>Vitamin C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must meet all the of following criteria to be included in this study:&#xD;
&#xD;
          -  Men residing in dormitory aged 21-60 years&#xD;
&#xD;
          -  Willing and able to give informed consent&#xD;
&#xD;
          -  Able to understand instructions and consume study medications according to the study&#xD;
             protocol.&#xD;
&#xD;
          -  Weight more than 40kg&#xD;
&#xD;
          -  Owns a mobile phone (with wireless fidelity and/or 3G connection and able to fill in&#xD;
             online forms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects who have any of the following criteria at baseline will be excluded from&#xD;
        participating in this study:&#xD;
&#xD;
          -  Symptoms of acute respiratory illness (e.g. fever, runny nose, sore throat, cough,&#xD;
             breathlessness, loss of smell and loss of taste) for the past 30 days&#xD;
&#xD;
          -  Known current or history of SARS-CoV-2 infection&#xD;
&#xD;
          -  Unable to read English or any of the available local languages used for this clinical&#xD;
             trial&#xD;
&#xD;
          -  History of cardiac or neurological diseases&#xD;
&#xD;
          -  History of retinal diseases&#xD;
&#xD;
          -  History of diabetes on insulin treatment&#xD;
&#xD;
          -  History of depression&#xD;
&#xD;
          -  History of chronic alcohol use&#xD;
&#xD;
          -  History of renal or hepatic dysfunction&#xD;
&#xD;
          -  History of glucose-6-phosphate dehydrogenase deficiency&#xD;
&#xD;
          -  History of anaemia, after exposure to any given medications&#xD;
&#xD;
          -  History of thyroid disorder, hyperthyroidism, or sensitivity to iodine&#xD;
&#xD;
          -  History of allergies with systemic presentation to any given medication (e.g.:&#xD;
             swelling of the face, throat, eyes and lips, respiratory disturbances, asthmatic&#xD;
             attacks, widespread skin blistering or urticaria (hives))&#xD;
&#xD;
          -  Concomitant medication that may lead to cardiac arrhythmia (azithromycin,&#xD;
             amitriptyline, cimetidine, citalopram, nortriptyline, pantoprazole, quetiapine etc).&#xD;
&#xD;
          -  Unwilling to comply with study dosing, instructions or restrictions.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Tuas South Dormitory</name>
      <address>
        <city>Singapore</city>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 24, 2020</study_first_posted>
  <last_update_submitted>October 13, 2020</last_update_submitted>
  <last_update_submitted_qc>October 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </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>Hydroxychloroquine</mesh_term>
    <mesh_term>Ivermectin</mesh_term>
    <mesh_term>Povidone-Iodine</mesh_term>
    <mesh_term>Povidone</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/NCT04446104
org study id: 2020/00561
nct id: NCT04446104
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
In December 2019, a novel coronavirus, now called COVID-19, emerged as a global health threat
      from Wuhan, China. Within weeks, the contagious virus spread within and between communities,
      causing a lower respiratory tract infection dominated by symptoms of fever, cough and sore
      throat. The incubation period was estimated at between 5 to 7 days, but could last as long as
      14 days. Although COVID-19 causes a mostly mild and self-limiting disease, respiratory
      involvement has been reported in about 5% of the population, requiring supplemental oxygen
      and even ventilatory support to relieve hypoxia. Alveolar damage, fibrosis and consolidation
      have been reported in radiologic and post-mortem studies. Existing data suggest a mortality
      rate of COVID-19 is approximately 1-2%, higher among individuals with pre-existing
      comorbidities and in healthcare systems with suboptimal access to ventilatory support.

      Given its high transmissibility, COVID-19 has quickly spread across the globe within a short
      interval. By 27 April 2020, over 3 million people around the world have been diagnosed with
      COVID-19, and more 200,000 have succumbed to the disease. As a proportion of patients
      manifest mild or no symptoms, these numbers are likely an underestimate of the actual number
      of patients with COVID-19. More disconcertingly, patients are known to shed viruses despite
      mild or no symptoms, making it essential that a collective approach against COVID-19
      incorporate active pharmacological treatment to prevent or mitigate virus pathogenesis prior
      to its potential evolution to cause respiratory distress. To date, clinical trials have
      focused on the treatment of hospitalised patients diagnosed with COVID-19; only few have
      examined the clinical benefits of pharmacological agents despite few compelling in vitro
      data.

      The relatively high transmission of COVID-19 in a closed dormitory environment of migrant
      workers in Singapore presents a real-life scenario where a prophylaxis treatment could reduce
      the impact of the disease. In Singapore, there are well grounded concerns an excess in cases
      could pose the possibility of strain in healthcare system and mentally drain her workers. The
      availability of an effective prophylaxis treatment is highly desirable to potentially reduce
      this burden. Data from the current study could also have implications on how future outbreaks
      in high-density areas should be managed, especially when residents are subjected to
      quarantine and isolation.
This is a pragmatic, open-label, randomised study with 4 interventional and 1 control arms.
      Individuals will be recruited from migrant worker dormitories, and written informed consent
      taken prior to enrolment. Randomisation will be done by the level within the dormitory
      building and predetermined each day according to a randomisation schema done by an
      independent statistician. This will obviate the potential for bias due to drug exchange
      between study individuals.

      The 5 arms consist of:

        -  Experimental arms

             1. Hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days
                (1,000 study subjects)

             2. Ivermectin tablet 12mg single dose (1,000 study subjects)

             3. Zinc tablet 80 mg/vitamin C 500mg daily for 42 days (1,000 study subjects)

             4. Povidone-iodine throat spray (3 times daily) for 42 days (1,000 study subjects)

        -  Control arm 5) Vitamin C tablet 500mg daily for 42 days (1,000 study subjects)

      Study information sheet will be circulated in selected buildings within the dormitory 1-4
      days before recruitment starts. All publicity materials and informed consent form will be
      translated to the different languages (e.g. Tamil, Bengali, Chinese, Burmese and Malay). A
      translator will be present to aid translation if necessary. Study subjects will be given
      ample time to ask questions relating to the study. Prospective participants will respond by
      showing up to recruitment stations at designated dates and times. Facilitators from the
      dormitory will be engaged to assist with the ground crowd-control. Prospective videos will be
      shown to inform the subject on the purpose, study inclusion and exclusion criteria, study
      medications, blood taking, reporting of adverse effects and follow-up visits. Informed
      consent will be taken before all study-related procedures are performed, including study
      eligibility. Translators will also help translate the daily questionnaires.

      During the baseline recruitment,

        1. History of symptoms, comorbidities and prior illnesses will be asked. Specific questions
           include presence or absence of the following symptoms: Fever, chills, myalgia, headache,
           diarrhoea, running nose, anosmia, loss of taste, sore throat, dry cough, shortness of
           breath.

        2. Measurements of study subjects' parameters such as weight, height, temperature, pulse
           rate and blood pressure will be recorded. Subjects randomised to Ivermectin arm and
           subsequently found to weigh below 60 kg will be randomised to other treatment arms.
           Subjects randomised to hydroxychloroquine arm and found to have systolic blood pressure
           >150 mmHg and/or diastolic blood pressure >90 mmHg and/or heart rate >100 beats per
           minute will also be randomized to other treatment arms.

        3. 12-lead electrocardiogram (ECG) will be performed in patients randomised to receive
           hydroxychloroquine. Only those with corrected QT values less than 450 ms, no cardiac
           arrhythmia and no ventricular hypertrophy will be allowed to receive hydroxychloroquine.
           Those with corrected QT values more than 450 ms, cardiac arrhythmia and ventricular
           hypertrophy will be randomised to other treatment arms.

        4. Blood sample (20 mL) will be obtained to test Immunoglobulin G/M against SARS-CoV-2.
           Depending on the findings, additional tests will be performed to explore potential
           biological reasons underpinning these observations. The choice of markers may include
           pathway-specific biomarkers targeting inflammation, oxidative stress, lipid parameters,
           as well as organ-specific ones such as renal and liver parameters. Given the large
           sample size and high costs of analysis, the study team will prioritise more detailed
           investigations in a targeted group of patients depending on the final findings. None of
           these blood results is a screening criteria for study participation. The investigator
           will share abnormal to the study subjects abnormal results of their renal and liver
           parameters should these tests are tested following study completion. The extent on
           investigation, however, depends on funding support. In this study, renal and hepatic
           dysfunction will be based on physician-diagnosed and self-declaration on the part of the
           study subject. All clinical information will be verified by a senior physician on-site.

        5. Study medications will be packed with clear instructions written on the packing bag. The
           package will be distributed to each subject based on the randomised treatment assigned.

        6. Study participants will be given a study card to remind them to submit their symptoms
           daily and to record the times when they consume their medications. They will also be
           asked to present this card to doctors at the medical post or hospital should they seek
           medical assistance. In the events of acute respiratory infection and hospitalization,
           lab testing will be done as clinically indicated. Subjects on ventilator support who are
           not able to take oral medications may discontinue taking the study drug. However,
           subjects will remain in the study for collection of data on duration of mechanical
           ventilation for analysis.

      During final study visit,

        1. The study team, including investigators, will be present at the dormitory. A repeated
           blood sample (20mL) will be collected for serological tests. Measurements of study
           subjects' parameters such as weight (using Tanita BC-418 and Tanita BC-420MA for
           bio-electrical impedance analysis), height, blood pressure will be taken. ECG will be
           done only for subjects in hydroxychloroquine arm. History will be taken including
           symptoms of fever, chills, myalgia, headache, diarrhoea, running nose, anosmia, loss of
           taste, sore throat, dry cough, shortness of breath and the duration of such symptoms, if
           any.

        2. Balance medication and packaging retrieval to do medication accounting and checking for
           adherence to assigned treatment arm

        3. Discharged from study if no adverse events to follow-up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Acute respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
description: Acute respiratory illness is defined by acute onset with any key respiratory symptoms including cough, shortness of breath, sore throat, runny nose and change in smell.
measure: Febrile respiratory illness in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Rate of hospitalization for COVID-19 and non-COVID-19 related indications in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Rate of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Duration of oxygen supplementation and mechanical ventilation in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Length of hospital stay in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Rate of laboratory-confirmed COVID-19 in treatment arms (hydroxychloroquine, ivermectin, zinc and povidone iodine)
time frame: At the end of study dosing, which is day 42
measure: Adverse events and serious adverse events in control arm (Vitamin C)
time frame: At the end of study dosing, which is day 42
measure: Drug discontinuation due to adverse events in control arm (Vitamin C)
time frame: At the end of study dosing, which is day 42
arm group label: Hydroxychloroquine
arm group type: Experimental
description: Participants will receive hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days
arm group label: Ivermectin
arm group type: Experimental
description: Participants will receive ivermectin tablet 12mg single dose
arm group label: Zinc/ Vitamin C
arm group type: Experimental
description: Participants will receive zinc tablet 80 mg/vitamin C 500mg daily for 42 days
arm group label: Povidone-iodine throat spray
arm group type: Experimental
description: Participants will receive povidone-iodine throat spray (3 times daily) for 42 days
arm group label: Vitamin C
arm group type: Active Comparator
description: Participants will receive vitamin C tablet 500mg daily for 42 days
intervention type: Drug
intervention name: Hydroxychloroquine Sulfate Tablets
description: Hydroxychloroquine tablet 400mg loading dose, followed by 200mg daily for 42 days
arm group label: Hydroxychloroquine
intervention type: Drug
intervention name: Ivermectin 3mg Tab
description: Ivermectin tablet 12mg single dose
arm group label: Ivermectin
intervention type: Drug
intervention name: Zinc
description: Zinc tablet 80 mg/vitamin C 500mg daily for 42 days
arm group label: Zinc/ Vitamin C
intervention type: Drug
intervention name: Povidone-Iodine
description: Povidone-iodine throat spray (3 times daily) for 42 days
arm group label: Povidone-iodine throat spray
intervention type: Dietary Supplement
intervention name: Vitamin C
description: Vitamin C tablet 500mg daily for 42 days
arm group label: Vitamin C
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Hydroxychloroquine
mesh term: Ivermectin
mesh term: Povidone-Iodine
mesh term: Povidone
sharing ipd: No