<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/NCT04412395</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-19_LF</org_study_id>
    <nct_id>NCT04412395</nct_id>
  </id_info>
  <brief_title>Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory in Treating COVID-19 Disease</brief_title>
  <acronym>COVID-19_LF</acronym>
  <official_title>Clinical Assessment of Oral Lactoferrin as a Safe Antiviral and Immunoregulatory Therapy in Patients Diagnosed With COVID-19 Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Research Centre, Egypt</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Egyptian Military Medical Services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National Research Centre, Egypt</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for&#xD;
      treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19&#xD;
      patients. The study was approved by the ethical committee of the Egyptian Center for Research&#xD;
      and Regenerative Medicine in 11-5-2020.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The World Health Organization (WHO) declared the coronavirus (SARS-CoV-2, COVID-19) outbreak&#xD;
      a Public Health Emergency of International Concern with a pandemic spread. The situation is&#xD;
      rapidly evolving, which raises the approach of reproposing already approved drugs to meet the&#xD;
      emerging challenge and to save time and money. Lactoferrin (Lf) is a natural glycoprotein&#xD;
      that broadly distributed within the body fluids and found predominantly in milk. It&#xD;
      represents a known component of the innate immune system. The antiviral activity of Lf has&#xD;
      been reported against many viruses, including SARS-CoV-1, through blocking the viral&#xD;
      receptors on the host cells preventing them from entry and replication. Markedly, data&#xD;
      reveals that Lf interacts with Heparan Sulfate Proteoglycans (HSPGs) and Angiotensin&#xD;
      Converting Enzyme 2 (ACE2) receptors that are reported as SARS-CoV-2-binding sites to enter&#xD;
      the host cell, suggesting a potential significance of Lf as an antiviral against SARS-CoV-2.&#xD;
      Moreover, the immunoregulatory effects of Lf can protect against the cytokine-storm and&#xD;
      thrombotic complications that result from the COVID-19-induced over-stimulated inflammatory&#xD;
      response and exaggerated immune reactions. In addition, Lf can decrease the free iron&#xD;
      toxicity caused by the virus as it has a strong iron chelating ability. Lf is a safe approved&#xD;
      food supplement that is available in the markets for enhancement of immunity and for&#xD;
      treatment of anemia. The aim of this study is to perform a randomized, double-blind,&#xD;
      placebo-controlled, two arms, clinical trial to assess oral enteric-coated tablet of bovine&#xD;
      apolactoferrin (the low iron-content form of Lf) as a safe antiviral and immunoregulatory&#xD;
      therapy in patients diagnosed with COVID-19 disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">February 1, 2022</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2022</primary_completion_date>
  <phase>Phase 2</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>Randomized, double-blind, placebo-controlled, clinical trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival rate.</measure>
    <time_frame>up to 8 weeks.</time_frame>
    <description>Comparing the influence of the intervention on the Survival rate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rate of disease remission.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT&#xD;
- For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )&gt; 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The number of patients with PCR negative results.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Comparing the influence of the intervention on the PCR negative results.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in the disease severity (clinical assessment).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes from severe to moderate or mild and the time taken.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in blood pressure.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in blood pressure mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in heart beats.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in heart rate in beat/second.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in body temperature.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in body temperature in Celsius.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in body respiratory rate.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in the respiratory rate in breath/minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in oxygen saturation.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in arterial oxygen saturation in mmHg.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in complete blood picture (CBC).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in complete blood picture (CBC) in cells per liter.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in C reactive protein (CRP).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in C reactive protein (CRP) in mg/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in erythrocyte sedimentation rate (ESR).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in D-dimer.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in D-dimer in ng/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in ferritin.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in ferritin in ng/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in liver Albumin.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in liver Albumin in g/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in total and direct Bilirubin.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in total and direct Bilirubin in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in aspartate aminotransferase (AST).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in aspartate aminotransferase (AST) in IU/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Alanine Aminotransferase (ALT).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in Alanine Aminotransferase (ALT) in IU/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Blood Urea Nitrogen (BUN).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Serum Creatinine.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in Serum Creatinine in mg/dL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Serum Creatinine clearance.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in Serum Creatinine in ml/min.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Glomerular filtration rate (GFR ).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in serum interleukin-1 (IL-1).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in interleukin-1 (IL-1) in pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in serum interleukin-6 (IL-6).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in interleukin-6 (IL-6) in pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in serum interleukin-10 (IL-10).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in interleukin-10 (IL-10) in pg/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in serum tumor necrosis factor-alpha (TNF alpha).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean changes in immunoglobulin G (IgG).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in immunoglobulin G (IgG) in ng/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean changes in immunoglobulin M (IgM).</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in immunoglobulin M (IgM) in ng/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The mean change in PCR viral load.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in PCR viral load in copies/mL.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in lung CT manifestation.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes in lung CT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nature and severity of Adverse Events.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording any unexpected Adverse Events of the intervention.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time for lung recovery.</measure>
    <time_frame>up to 8 weeks.</time_frame>
    <description>Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of missed drug doses among each treatment group.</measure>
    <time_frame>up to 4 weeks.</time_frame>
    <description>Recording the changes the event of missed drug doses.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">516</enrollment>
  <condition>Corona Virus Infection</condition>
  <condition>Middle East Respiratory Syndrome (MERS)</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>Coronavirus Infection</condition>
  <condition>COVID-19</condition>
  <condition>SARS-CoV 2</condition>
  <arm_group>
    <arm_group_label>Arm 01 (SOC + Lactoferrin 1200 mg QID)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to this group will receive two 600 mg Lactoferrin tablets QID plus the Standard of Care (SOC) treatment(s).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 02 (SOC + Placebo QID)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients randomized to this group will receive two placebo tablets QID plus the SOC treatment(s).</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Lactoferrin (Apolactoferrin)</intervention_name>
    <description>Apolactoferrin is an iron-free Lactoferrin (with very low iron saturation). Lactoferrin (Lf) is a natural glycoprotein that is found predominantly in milk. Lf represents a known component of the innate immune system present in neutrophil-specific granules and broadly distributed within the body fluids and exocrine secretions.</description>
    <arm_group_label>Arm 01 (SOC + Lactoferrin 1200 mg QID)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo of excipient(s) will be administered</intervention_name>
    <description>Placebo of the equivalent excipient will be administered to placebo group</description>
    <arm_group_label>Arm 02 (SOC + Placebo QID)</arm_group_label>
    <other_name>excipient(s)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients tested positive (PCR) for SARS-CoV-2 and clinically symptomatic.&#xD;
&#xD;
          -  Adult patients with age &gt;18 years.&#xD;
&#xD;
          -  Patients willing and able to sign the study informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Critically severe disease patients (having Respiratory failure requiring mechanical&#xD;
             ventilation, or signs of septic shock or multiple organ failure requiring ICU&#xD;
             admission).&#xD;
&#xD;
          -  Patients who are unconscious&#xD;
&#xD;
          -  Patients who have convulsions&#xD;
&#xD;
          -  Patients suffering from central cyanosis with SPO2&lt; 90% (for asthmatic patients with&#xD;
             SPO2&lt;88%)&#xD;
&#xD;
          -  Pregnant or lactating women&#xD;
&#xD;
          -  Patients with a known history of pro-inflammatory diseases (patients with autoimmune&#xD;
             diseases, patients receiving chemotherapy for cancer, patients with malabsorption,&#xD;
             patients with inflammatory bowel disease, Crohn's disease or ulcerative colitis).&#xD;
&#xD;
          -  History or suspected immunosuppressive or immunodeficient state including HIV&#xD;
             infection, or chronic immunosuppressant medication (more than 14 days) within the past&#xD;
             3 months (inhaled and topical steroids are allowed).&#xD;
&#xD;
          -  Patients with severe renal impairment (GFR &lt;60 ml/min/1.73m2 as measured by the&#xD;
             Cockcroft-Gault formula).&#xD;
&#xD;
          -  Patient with severe hepatic impairment, biliary cirrhosis or cholestasis&#xD;
&#xD;
          -  Patients who received immunoregulatory therapy within one month before the start of&#xD;
             the study.&#xD;
&#xD;
          -  Patients with Known or suspected allergy or any contraindications to Lactoferrin.&#xD;
&#xD;
          -  Any condition, according to the judgment of the investigator, would interfere with the&#xD;
             patient's ability to comply with all study requirements or that would place the&#xD;
             patient at unacceptable risk by his/her participation in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rehab Hegazy, PhD</last_name>
    <role>Study Director</role>
    <affiliation>National Research Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rehab Hegazy, PhD</last_name>
    <phone>+201001507676</phone>
    <email>rehab_hegazy@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Osama Azmy, MD</last_name>
    <phone>+201223103084</phone>
    <email>osamaazmy@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>National Research Center, Egypt (Clinical and Molecular Pharmacology)</name>
      <address>
        <city>Cairo</city>
        <state>Giza</state>
        <zip>12622</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <contact>
      <last_name>Marawan Abdelbaset, PhD</last_name>
      <phone>+0201002227202</phone>
      <email>dr.marawan@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Bassim Mohamed, PhD</last_name>
      <email>Bassim.mohamed@umontreal.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Marawan Abdelbaset, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Bassim Mohamed, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinmax CRO (Clinical Research Organization)</name>
      <address>
        <city>Cairo</city>
        <zip>11835</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <contact>
      <last_name>Khaled Prince, B Pharm</last_name>
      <phone>+20106725802</phone>
      <email>Khaled.prince@clinmax.net</email>
    </contact>
    <contact_backup>
      <last_name>Christine Gindy, B Pharm</last_name>
      <email>christine.gindy@clinmax.net</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Unit National Research Center</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
    <contact>
      <last_name>Wafaa Abdel Aal, MD</last_name>
    </contact>
    <contact_backup>
      <last_name>Osama Azmy, MD</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Egyptian Military Medical Services (Hospitals)</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 15, 2020</study_first_submitted>
  <study_first_submitted_qc>May 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>November 12, 2021</last_update_submitted>
  <last_update_submitted_qc>November 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Research Centre, Egypt</investigator_affiliation>
    <investigator_full_name>Rehab Ragab Hegazy</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Lactoferrin</keyword>
  <keyword>Apolactoferrin</keyword>
  <keyword>Immuno-modulatory</keyword>
  <keyword>Cytokine-storm</keyword>
  <keyword>Antiviral</keyword>
  <keyword>2019nCoV</keyword>
  <keyword>2019 new coronavirus (2019nCoV)</keyword>
  <keyword>Middle East Respiratory Syndrome (MERS)</keyword>
  <keyword>Acute Respiratory Distress Syndrome (ARDS)</keyword>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV 2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactoferrin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Not yet decided.</ipd_description>
    <ipd_time_frame>within 6 month</ipd_time_frame>
    <ipd_access_criteria>all valid data</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/NCT04412395
org study id: COVID-19_LF
nct id: NCT04412395
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of the study is to clinically use bovine Lf as a safe antiviral adjuvant for
      treatment and to assess the potential in reducing mortality and morbidity rates in COVID-19
      patients. The study was approved by the ethical committee of the Egyptian Center for Research
      and Regenerative Medicine in 11-5-2020.
The World Health Organization (WHO) declared the coronavirus (SARS-CoV-2, COVID-19) outbreak
      a Public Health Emergency of International Concern with a pandemic spread. The situation is
      rapidly evolving, which raises the approach of reproposing already approved drugs to meet the
      emerging challenge and to save time and money. Lactoferrin (Lf) is a natural glycoprotein
      that broadly distributed within the body fluids and found predominantly in milk. It
      represents a known component of the innate immune system. The antiviral activity of Lf has
      been reported against many viruses, including SARS-CoV-1, through blocking the viral
      receptors on the host cells preventing them from entry and replication. Markedly, data
      reveals that Lf interacts with Heparan Sulfate Proteoglycans (HSPGs) and Angiotensin
      Converting Enzyme 2 (ACE2) receptors that are reported as SARS-CoV-2-binding sites to enter
      the host cell, suggesting a potential significance of Lf as an antiviral against SARS-CoV-2.
      Moreover, the immunoregulatory effects of Lf can protect against the cytokine-storm and
      thrombotic complications that result from the COVID-19-induced over-stimulated inflammatory
      response and exaggerated immune reactions. In addition, Lf can decrease the free iron
      toxicity caused by the virus as it has a strong iron chelating ability. Lf is a safe approved
      food supplement that is available in the markets for enhancement of immunity and for
      treatment of anemia. The aim of this study is to perform a randomized, double-blind,
      placebo-controlled, two arms, clinical trial to assess oral enteric-coated tablet of bovine
      apolactoferrin (the low iron-content form of Lf) as a safe antiviral and immunoregulatory
      therapy in patients diagnosed with COVID-19 disease.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, double-blind, placebo-controlled, clinical trial.
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Survival rate.
time frame: up to 8 weeks.
description: Comparing the influence of the intervention on the Survival rate.
measure: Rate of disease remission.
time frame: up to 4 weeks.
description: For mild/moderate symptoms patients: fever, cough and other symptoms relieved with improved lung CT
- For severe symptoms patients: fever, cough and other symptoms relieved with improved lung CT, and oxygen saturation by pulse oximetry (SPO2 )> 93% for nonasthmatic patients, and from 88-92% in asthmatic patients.
measure: The number of patients with PCR negative results.
time frame: up to 4 weeks.
description: Comparing the influence of the intervention on the PCR negative results.
measure: Mean change in the disease severity (clinical assessment).
time frame: up to 4 weeks.
description: Recording the changes from severe to moderate or mild and the time taken.
measure: Mean change in blood pressure.
time frame: up to 4 weeks.
description: Recording the changes in blood pressure mmHg.
measure: Mean change in heart beats.
time frame: up to 4 weeks.
description: Recording the changes in heart rate in beat/second.
measure: Mean change in body temperature.
time frame: up to 4 weeks.
description: Recording the changes in body temperature in Celsius.
measure: Mean change in body respiratory rate.
time frame: up to 4 weeks.
description: Recording the changes in the respiratory rate in breath/minute.
measure: Mean change in oxygen saturation.
time frame: up to 4 weeks.
description: Recording the changes in arterial oxygen saturation in mmHg.
measure: Mean change in the ratio in arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
time frame: up to 4 weeks.
description: Recording the changes in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio).
measure: Mean change in complete blood picture (CBC).
time frame: up to 4 weeks.
description: Recording the changes in complete blood picture (CBC) in cells per liter.
measure: Mean change in C reactive protein (CRP).
time frame: up to 4 weeks.
description: Recording the changes in C reactive protein (CRP) in mg/L.
measure: Mean change in erythrocyte sedimentation rate (ESR).
time frame: up to 4 weeks.
description: Recording the changes in erythrocyte sedimentation rate (ESR) in mm/hr.
measure: Mean change in D-dimer.
time frame: up to 4 weeks.
description: Recording the changes in D-dimer in ng/mL.
measure: Mean change in ferritin.
time frame: up to 4 weeks.
description: Recording the changes in ferritin in ng/mL.
measure: Mean change in liver Albumin.
time frame: up to 4 weeks.
description: Recording the changes in liver Albumin in g/L.
measure: Mean change in total and direct Bilirubin.
time frame: up to 4 weeks.
description: Recording the changes in total and direct Bilirubin in mg/dL.
measure: Mean change in prothrombin time (PT) and partial thromboplastin time (PTT ).
time frame: up to 4 weeks.
description: Recording the changes in prothrombin time (PT), partial thromboplastin time (PTT ) in seconds and calculating International Normalized Ratio (INR).
measure: Mean change in aspartate aminotransferase (AST).
time frame: up to 4 weeks.
description: Recording the changes in aspartate aminotransferase (AST) in IU/L.
measure: Mean change in Alanine Aminotransferase (ALT).
time frame: up to 4 weeks.
description: Recording the changes in Alanine Aminotransferase (ALT) in IU/L.
measure: Mean change in Blood Urea Nitrogen (BUN).
time frame: up to 4 weeks.
description: Recording the changes in Blood Urea Nitrogen (BUN) in mg/dL.
measure: Mean change in Serum Creatinine.
time frame: up to 4 weeks.
description: Recording the changes in Serum Creatinine in mg/dL.
measure: Mean change in Serum Creatinine clearance.
time frame: up to 4 weeks.
description: Recording the changes in Serum Creatinine in ml/min.
measure: Mean change in Glomerular filtration rate (GFR ).
time frame: up to 4 weeks.
description: Recording the changes in Glomerular filtration rate (GFR ) ml/min/m2.
measure: The mean change in serum interleukin-1 (IL-1).
time frame: up to 4 weeks.
description: Recording the changes in interleukin-1 (IL-1) in pg/ml.
measure: The mean change in serum interleukin-6 (IL-6).
time frame: up to 4 weeks.
description: Recording the changes in interleukin-6 (IL-6) in pg/ml.
measure: The mean change in serum interleukin-10 (IL-10).
time frame: up to 4 weeks.
description: Recording the changes in interleukin-10 (IL-10) in pg/ml.
measure: The mean change in serum tumor necrosis factor-alpha (TNF alpha).
time frame: up to 4 weeks.
description: Recording the changes in tumor necrosis factor-alpha (TNF alpha) in ng/ml.
measure: Mean changes in immunoglobulin G (IgG).
time frame: up to 4 weeks.
description: Recording the changes in immunoglobulin G (IgG) in ng/ml.
measure: Mean changes in immunoglobulin M (IgM).
time frame: up to 4 weeks.
description: Recording the changes in immunoglobulin M (IgM) in ng/ml.
measure: The mean change in PCR viral load.
time frame: up to 4 weeks.
description: Recording the changes in PCR viral load in copies/mL.
measure: Mean change in lung CT manifestation.
time frame: up to 4 weeks.
description: Recording the changes in lung CT.
measure: Nature and severity of Adverse Events.
time frame: up to 4 weeks.
description: Recording any unexpected Adverse Events of the intervention.
measure: Time for lung recovery.
time frame: up to 8 weeks.
description: Recording the changes (the average time of lung imaging recovery), as assessed by lung CT.
measure: The number of missed drug doses among each treatment group.
time frame: up to 4 weeks.
description: Recording the changes the event of missed drug doses.
arm group label: Arm 01 (SOC + Lactoferrin 1200 mg QID)
arm group type: Active Comparator
description: Patients randomized to this group will receive two 600 mg Lactoferrin tablets QID plus the Standard of Care (SOC) treatment(s).
arm group label: Arm 02 (SOC + Placebo QID)
arm group type: Placebo Comparator
description: Patients randomized to this group will receive two placebo tablets QID plus the SOC treatment(s).
intervention type: Dietary Supplement
intervention name: Lactoferrin (Apolactoferrin)
description: Apolactoferrin is an iron-free Lactoferrin (with very low iron saturation). Lactoferrin (Lf) is a natural glycoprotein that is found predominantly in milk. Lf represents a known component of the innate immune system present in neutrophil-specific granules and broadly distributed within the body fluids and exocrine secretions.
arm group label: Arm 01 (SOC + Lactoferrin 1200 mg QID)
intervention type: Drug
intervention name: Placebo of excipient(s) will be administered
description: Placebo of the equivalent excipient will be administered to placebo group
arm group label: Arm 02 (SOC + Placebo QID)
other name: excipient(s)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Rehab Hegazy, PhD
role: Study Director
affiliation: National Research Center
last name: Rehab Hegazy, PhD
phone: +201001507676
email: rehab_hegazy@hotmail.com
last name: Osama Azmy, MD
phone: +201223103084
email: osamaazmy@yahoo.com
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country: Egypt
responsible party type: Principal Investigator
investigator affiliation: National Research Centre, Egypt
investigator full name: Rehab Ragab Hegazy
investigator title: Assistant Professor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Syndrome
mesh term: Lactoferrin
sharing ipd: Yes
ipd description: Not yet decided.
ipd time frame: within 6 month
ipd access criteria: all valid data