<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/NCT04461340</url>
  </required_header>
  <id_info>
    <org_study_id>sirolimus in COVID 19</org_study_id>
    <nct_id>NCT04461340</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Sirolimus in COVID-19 Infection</brief_title>
  <official_title>Efficacy and Safety of Sirolimus for Treating COVID-19 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexandria University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alexandria University</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>
      This research is planned to illustrate the efficacy and safety of sirolimus as an adjuvant&#xD;
      agent to the standard treatment protocol against COVID-19 infection&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In early December 2019, several pneumonia cases of unknown origin were observed in Wuhan&#xD;
      (China). A novel enveloped RNA β coronavirus was isolated and named severe acute respiratory&#xD;
      syndrome coronavirus 2 (SARSCoV- 2). The new virus rapidly spread across China and worldwide.&#xD;
      On March 11th 2020, the World Health Organization (WHO) declared coronavirus disease 2019&#xD;
      (COVID-19) a pandemic. As of 1July 2020, COVID-19 has been confirmed in 10,357,662&#xD;
      individuals globally with deaths reaching 508,055 with a morality of 5.37%. Egypt has 68,311&#xD;
      confirmed cases and 2935 deaths.&#xD;
&#xD;
      The virus mainly spreads through respiratory droplets from infected patients. The clinical&#xD;
      spectrum of COVID-19 infection ranges from asymptomatic forms to severe pneumonia requiring&#xD;
      hospitalization and isolation in critical care units with the need of mechanical ventilation&#xD;
      due to acute respiratory distress syndrome (ARDS). Main symptoms include fever, fatigue and&#xD;
      dry cough. Common laboratory findings include lymphopenia and elevated lactate dehydrogenase&#xD;
      levels. Platelet count is usually normal or mildly decreased. C reactive protein (CRP) and&#xD;
      erythrocyte sedimentation rate (ESR) are usually increased while procalcitonin levels are&#xD;
      normal and elevation of procalcitonin usually indicates secondary bacterial infection.&#xD;
      Ferritin, D-dimer, and creatine kinase elevation is associated with severe disease. Chest&#xD;
      computed tomographic scans show a typical pattern of bilateral patchy shadows or ground glass&#xD;
      opacity.&#xD;
&#xD;
      Severe COVID-19 conditions are usually due to an aggressive inflammatory response known as&#xD;
      &quot;cytokine storm&quot; that is characterized by the release of a large amount of pro-inflammatory&#xD;
      cytokines. Lung injury, multiorgan failure, and unfavorable prognosis of severe COVID-19&#xD;
      infection have been attributed mainly to the cytokine storm state.&#xD;
&#xD;
      Many proinflammatory cytokines elevate in COVID-19 patients including interleukin (IL)-1,&#xD;
      IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α and interferon( IFN)-Ȣ stimulating immune&#xD;
      cells to invade sites of infection causing endothelial dysfunction, vascular damage, alveolar&#xD;
      damage and ARDS. Cytokine storm has been reported in several viral infections including&#xD;
      influenza H5N1 virus, influenza H1N1 virus, and the two coronaviruses highly related to&#xD;
      COVID-19; &quot;SARS-CoV&quot; and &quot;MERSCoV&quot;.&#xD;
&#xD;
      Currently, there is no vaccine and/or specific therapeutic drugs targeting the SARS-CoV-2.&#xD;
      Hence, it remains a major challenge to decide what potential therapeutic regimens to prevent&#xD;
      and treat severe COVID-19 infections. Effective vaccines are essential to combat against the&#xD;
      extremely contagious SARS-CoV-2. Until we have specific vaccines or therapeutic drugs&#xD;
      targeting SARS-CoV-2, &quot;repurposed&quot; drugs have been used to treat COVID-19 patients. At&#xD;
      present, treatment of SARS-CoV-2 infection are mainly repurposing the available therapeutic&#xD;
      drugs and based on symptomatic conditions. Considering ARDS, followed by secondary&#xD;
      infections, antibiotics, antiviral therapy, systemic corticosteroids, and anti-inflammatory&#xD;
      drugs (including anti-arthritis drugs) are often used in the treatment regimens.&#xD;
      Neuraminidase inhibitors, RNA synthesis inhibitors, convalescent plasma, and traditional&#xD;
      herbal medicines have also been utilized in the treatment of COVID 19. Nevertheless, the&#xD;
      efficacy of these treatment regimens remains to be verified by appropriately designed&#xD;
      clinical trials. Sirolimus, also known as rapamycin, is an immunosuppressant that is used to&#xD;
      prevent organ transplant rejection by inhibiting mammalian target of rapamycin (mTOR) kinase.&#xD;
      mTOR plays a key role in viral replication. In an in vitro experiment, sirolimus has been&#xD;
      shown to affect PI3K/AKT/mTOR pathway which inhibited MERS-CoV activity. Studies of patients&#xD;
      hospitalized with influenza can further shed light on the antiviral effect of sirolimus. In a&#xD;
      randomized clinical trial conducted on 38 patients with confirmed H1N1 pneumonia and on&#xD;
      mechanical ventilator support, a group treated with corticosteroids and 2 mg/day of sirolimus&#xD;
      for 14 days (N=19) showed significantly better clinical outcomes compared with the group&#xD;
      treated with corticosteroids only, including shorter median duration of ventilator used.&#xD;
      Delayed oseltamivir plus sirolimus treatment in pH1N1-infected mouse model further suggested&#xD;
      a significant association between the sirolimus treatment and improved outcomes. At least one&#xD;
      in silico study identified sirolimus as one of the 16 potential candidates for treating&#xD;
      COVID-19 patients based on data from other human coronavirus infections using network-based&#xD;
      drug repurposing model.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 15, 2020</start_date>
  <completion_date type="Anticipated">November 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2020</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>single-blinded randomized clinical trial in which participants will be randomly assigned to one of the study groups using block randomization with a ratio of 1:1.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to clinical recovery</measure>
    <time_frame>14-28 days</time_frame>
    <description>The duration from start of treatment to normalization of pyrexia, respiratory rate ,O2 saturation and relief of cough that is maintained for at least 72 hours.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Viral clearance</measure>
    <time_frame>14 days</time_frame>
    <description>Two successive negative COVID-19 PCR analysis tests 48-72 hours apart</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>radiological lung extension</measure>
    <time_frame>14 days</time_frame>
    <description>Evaluate the lung extension of pneumonia at day 14</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>drug adverse events</measure>
    <time_frame>28 days</time_frame>
    <description>incidence and type of adverse events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28 day mortality</measure>
    <time_frame>28 day</time_frame>
    <description>number of deaths to total number of patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>intensive care unit (ICU) admission rate</measure>
    <time_frame>28 days</time_frame>
    <description>deteriorated patients who need admission to intensive care unit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>28 days</time_frame>
    <description>duration from hospitalization to discharge</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20 patients will receive sirolimus ( oral dose of 6 mg on day 1 followed by 2 mg daily for 9 days) plus national standard of care therapy against COVID 19</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>20 patients will receive only national standard of care therapy against COVID 19</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>oral dose of 6 mg on day1 followed by 2 mg daily for 9 days</description>
    <arm_group_label>Group A</arm_group_label>
    <other_name>Rapamune</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults (˃18 years) COVID-19 positive patients (confirmed by PCR).&#xD;
&#xD;
          -  Moderate infection ( pneumonia ± leucopenia or lymphopenia ).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe or life threatening COVID infection: Severe disease is defined as: dyspnea,&#xD;
             respiratory frequency ≥ 30/min, blood oxygen saturation ≤ 93%, partial pressure of&#xD;
             arterial oxygen to fraction of inspired oxygen ratio &lt; 300, and/or lung infiltrates &gt;&#xD;
             50% within 24 to 48 hours. Life threatening disease is defined as: respiratory&#xD;
             failure, septic shock, and/or multiple organ dysfunction or failure .&#xD;
&#xD;
          -  Pregnant or lactating females.&#xD;
&#xD;
          -  Participation in any investigational clinical study, other than observational, within&#xD;
             the past 30 days; or plans to participate in such a study at any time from the day of&#xD;
             enrollment until 30 days post-treatment in the current study.&#xD;
&#xD;
          -  Allergy or hypersensitivity to sirolimus.&#xD;
&#xD;
          -  Taking immunosuppressive drugs.&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) &lt; 30 ml/min by CKD-EPI equation.&#xD;
&#xD;
          -  liver cirrhosis .&#xD;
&#xD;
          -  Decompensated heart failure.&#xD;
&#xD;
          -  known active tuberculosis (TB) or history of incompletely treated TB.&#xD;
&#xD;
          -  Uncontrolled systemic bacterial or fungal infections.&#xD;
&#xD;
          -  Drugs that may affect sirolimus level: antifungals, diltiazem, verapamil, nicardipine,&#xD;
             phenytoin, phenobarbital, rifampicin, carbamazepine.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohamed Mamdouh Elsayed, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>lecturer</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ayman I Baess, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Associate professor</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Heba M El weshahi, MD</last_name>
    <role>Study Chair</role>
    <affiliation>professor</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nermine H Zakaria, MD</last_name>
    <role>Study Chair</role>
    <affiliation>professor</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mohamed Mamdouh Elsayed, MD</last_name>
    <phone>00201068055103</phone>
    <email>dr_mohamedmamdouh87@yahoo.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ayman I Baess, MD</last_name>
    <phone>00201006822068</phone>
    <email>Ayman.baeis@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Faculty of Medicine, Alexandria university, Egypt</name>
      <address>
        <city>Alexandria</city>
        <zip>21526</zip>
        <country>Egypt</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mohamed Mamdouh Elsayed, MD</last_name>
      <phone>00201068055103</phone>
      <email>dr_mohamedmamdouh87@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <reference>
    <citation>Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:</citation>
    <PMID>31986264</PMID>
  </reference>
  <reference>
    <citation>Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.</citation>
    <PMID>31986261</PMID>
  </reference>
  <reference>
    <citation>Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020 Apr;87(4):281-286. doi: 10.1007/s12098-020-03263-6. Epub 2020 Mar 13.</citation>
    <PMID>32166607</PMID>
  </reference>
  <reference>
    <citation>Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.</citation>
    <PMID>32007143</PMID>
  </reference>
  <reference>
    <citation>Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available. Erratum In: Intensive Care Med. 2020 Apr 6;:</citation>
    <PMID>32125452</PMID>
  </reference>
  <reference>
    <citation>Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.</citation>
    <PMID>32217835</PMID>
  </reference>
  <reference>
    <citation>Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, Liu ZS. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr. 2020 Jun;16(3):251-259. doi: 10.1007/s12519-020-00354-4. Epub 2020 Mar 19.</citation>
    <PMID>32193831</PMID>
  </reference>
  <reference>
    <citation>Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.</citation>
    <PMID>28466096</PMID>
  </reference>
  <reference>
    <citation>Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020 Mar 16;14(1):69-71. doi: 10.5582/bst.2020.01020. Epub 2020 Jan 28.</citation>
    <PMID>31996494</PMID>
  </reference>
  <reference>
    <citation>Seto B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med. 2012 Nov 15;1(1):29. doi: 10.1186/2001-1326-1-29.</citation>
    <PMID>23369283</PMID>
  </reference>
  <reference>
    <citation>Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH, Olinger GG, Hensley LE, Jahrling PB. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015 Feb;59(2):1088-99. doi: 10.1128/AAC.03659-14. Epub 2014 Dec 8.</citation>
    <PMID>25487801</PMID>
  </reference>
  <reference>
    <citation>Wang CH, Chung FT, Lin SM, Huang SY, Chou CL, Lee KY, Lin TY, Kuo HP. Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure. Crit Care Med. 2014 Feb;42(2):313-21. doi: 10.1097/CCM.0b013e3182a2727d.</citation>
    <PMID>24105455</PMID>
  </reference>
  <reference>
    <citation>Jia X, Liu B, Bao L, Lv Q, Li F, Li H, An Y, Zhang X, Cao B, Wang C. Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog. 2018 Nov 13;14(11):e1007428. doi: 10.1371/journal.ppat.1007428. eCollection 2018 Nov.</citation>
    <PMID>30422993</PMID>
  </reference>
  <reference>
    <citation>Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14. doi: 10.1038/s41421-020-0153-3. eCollection 2020.</citation>
    <PMID>32194980</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 4, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>September 6, 2020</last_update_submitted>
  <last_update_submitted_qc>September 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Alexandria University</investigator_affiliation>
    <investigator_full_name>Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD</investigator_full_name>
    <investigator_title>lecturer</investigator_title>
  </responsible_party>
  <keyword>sirolimus</keyword>
  <keyword>COVID 19</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>Sirolimus</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04461340
org study id: sirolimus in COVID 19
nct id: NCT04461340
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This research is planned to illustrate the efficacy and safety of sirolimus as an adjuvant
      agent to the standard treatment protocol against COVID-19 infection
In early December 2019, several pneumonia cases of unknown origin were observed in Wuhan
      (China). A novel enveloped RNA β coronavirus was isolated and named severe acute respiratory
      syndrome coronavirus 2 (SARSCoV- 2). The new virus rapidly spread across China and worldwide.
      On March 11th 2020, the World Health Organization (WHO) declared coronavirus disease 2019
      (COVID-19) a pandemic. As of 1July 2020, COVID-19 has been confirmed in 10,357,662
      individuals globally with deaths reaching 508,055 with a morality of 5.37%. Egypt has 68,311
      confirmed cases and 2935 deaths.

      The virus mainly spreads through respiratory droplets from infected patients. The clinical
      spectrum of COVID-19 infection ranges from asymptomatic forms to severe pneumonia requiring
      hospitalization and isolation in critical care units with the need of mechanical ventilation
      due to acute respiratory distress syndrome (ARDS). Main symptoms include fever, fatigue and
      dry cough. Common laboratory findings include lymphopenia and elevated lactate dehydrogenase
      levels. Platelet count is usually normal or mildly decreased. C reactive protein (CRP) and
      erythrocyte sedimentation rate (ESR) are usually increased while procalcitonin levels are
      normal and elevation of procalcitonin usually indicates secondary bacterial infection.
      Ferritin, D-dimer, and creatine kinase elevation is associated with severe disease. Chest
      computed tomographic scans show a typical pattern of bilateral patchy shadows or ground glass
      opacity.

      Severe COVID-19 conditions are usually due to an aggressive inflammatory response known as
      "cytokine storm" that is characterized by the release of a large amount of pro-inflammatory
      cytokines. Lung injury, multiorgan failure, and unfavorable prognosis of severe COVID-19
      infection have been attributed mainly to the cytokine storm state.

      Many proinflammatory cytokines elevate in COVID-19 patients including interleukin (IL)-1,
      IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α and interferon( IFN)-Ȣ stimulating immune
      cells to invade sites of infection causing endothelial dysfunction, vascular damage, alveolar
      damage and ARDS. Cytokine storm has been reported in several viral infections including
      influenza H5N1 virus, influenza H1N1 virus, and the two coronaviruses highly related to
      COVID-19; "SARS-CoV" and "MERSCoV".

      Currently, there is no vaccine and/or specific therapeutic drugs targeting the SARS-CoV-2.
      Hence, it remains a major challenge to decide what potential therapeutic regimens to prevent
      and treat severe COVID-19 infections. Effective vaccines are essential to combat against the
      extremely contagious SARS-CoV-2. Until we have specific vaccines or therapeutic drugs
      targeting SARS-CoV-2, "repurposed" drugs have been used to treat COVID-19 patients. At
      present, treatment of SARS-CoV-2 infection are mainly repurposing the available therapeutic
      drugs and based on symptomatic conditions. Considering ARDS, followed by secondary
      infections, antibiotics, antiviral therapy, systemic corticosteroids, and anti-inflammatory
      drugs (including anti-arthritis drugs) are often used in the treatment regimens.
      Neuraminidase inhibitors, RNA synthesis inhibitors, convalescent plasma, and traditional
      herbal medicines have also been utilized in the treatment of COVID 19. Nevertheless, the
      efficacy of these treatment regimens remains to be verified by appropriately designed
      clinical trials. Sirolimus, also known as rapamycin, is an immunosuppressant that is used to
      prevent organ transplant rejection by inhibiting mammalian target of rapamycin (mTOR) kinase.
      mTOR plays a key role in viral replication. In an in vitro experiment, sirolimus has been
      shown to affect PI3K/AKT/mTOR pathway which inhibited MERS-CoV activity. Studies of patients
      hospitalized with influenza can further shed light on the antiviral effect of sirolimus. In a
      randomized clinical trial conducted on 38 patients with confirmed H1N1 pneumonia and on
      mechanical ventilator support, a group treated with corticosteroids and 2 mg/day of sirolimus
      for 14 days (N=19) showed significantly better clinical outcomes compared with the group
      treated with corticosteroids only, including shorter median duration of ventilator used.
      Delayed oseltamivir plus sirolimus treatment in pH1N1-infected mouse model further suggested
      a significant association between the sirolimus treatment and improved outcomes. At least one
      in silico study identified sirolimus as one of the 16 potential candidates for treating
      COVID-19 patients based on data from other human coronavirus infections using network-based
      drug repurposing model.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: single-blinded randomized clinical trial in which participants will be randomly assigned to one of the study groups using block randomization with a ratio of 1:1.
primary purpose: Treatment
masking: Single (Participant)
measure: Time to clinical recovery
time frame: 14-28 days
description: The duration from start of treatment to normalization of pyrexia, respiratory rate ,O2 saturation and relief of cough that is maintained for at least 72 hours.
measure: Viral clearance
time frame: 14 days
description: Two successive negative COVID-19 PCR analysis tests 48-72 hours apart
measure: radiological lung extension
time frame: 14 days
description: Evaluate the lung extension of pneumonia at day 14
measure: drug adverse events
time frame: 28 days
description: incidence and type of adverse events
measure: 28 day mortality
time frame: 28 day
description: number of deaths to total number of patients
measure: intensive care unit (ICU) admission rate
time frame: 28 days
description: deteriorated patients who need admission to intensive care unit
measure: Duration of hospital stay
time frame: 28 days
description: duration from hospitalization to discharge
arm group label: Group A
arm group type: Experimental
description: 20 patients will receive sirolimus ( oral dose of 6 mg on day 1 followed by 2 mg daily for 9 days) plus national standard of care therapy against COVID 19
arm group label: Group B
arm group type: No Intervention
description: 20 patients will receive only national standard of care therapy against COVID 19
intervention type: Drug
intervention name: Sirolimus
description: oral dose of 6 mg on day1 followed by 2 mg daily for 9 days
arm group label: Group A
other name: Rapamune
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mohamed Mamdouh Elsayed, MD
role: Principal Investigator
affiliation: lecturer
last name: Ayman I Baess, MD
role: Study Chair
affiliation: Associate professor
last name: Heba M El weshahi, MD
role: Study Chair
affiliation: professor
last name: Nermine H Zakaria, MD
role: Study Chair
affiliation: professor
last name: Mohamed Mamdouh Elsayed, MD
phone: 00201068055103
email: dr_mohamedmamdouh87@yahoo.com
last name: Ayman I Baess, MD
phone: 00201006822068
email: Ayman.baeis@yahoo.com
facility: 
status: Recruiting
contact: 
country: Egypt
citation: Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
PMID: 31986264
citation: Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, Xing F, Liu J, Yip CC, Poon RW, Tsoi HW, Lo SK, Chan KH, Poon VK, Chan WM, Ip JD, Cai JP, Cheng VC, Chen H, Hui CK, Yuen KY. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb 15;395(10223):514-523. doi: 10.1016/S0140-6736(20)30154-9. Epub 2020 Jan 24.
PMID: 31986261
citation: Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020 Apr;87(4):281-286. doi: 10.1007/s12098-020-03263-6. Epub 2020 Mar 13.
PMID: 32166607
citation: Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020 Feb 15;395(10223):507-513. doi: 10.1016/S0140-6736(20)30211-7. Epub 2020 Jan 30.
PMID: 32007143
citation: Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. No abstract available. Erratum In: Intensive Care Med. 2020 Apr 6;:
PMID: 32125452
citation: Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PMID: 32217835
citation: Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, Liu ZS. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study. World J Pediatr. 2020 Jun;16(3):251-259. doi: 10.1007/s12519-020-00354-4. Epub 2020 Mar 19.
PMID: 32193831
citation: Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017 Jul;39(5):529-539. doi: 10.1007/s00281-017-0629-x. Epub 2017 May 2.
PMID: 28466096
citation: Lu H. Drug treatment options for the 2019-new coronavirus (2019-nCoV). Biosci Trends. 2020 Mar 16;14(1):69-71. doi: 10.5582/bst.2020.01020. Epub 2020 Jan 28.
PMID: 31996494
citation: Seto B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin Transl Med. 2012 Nov 15;1(1):29. doi: 10.1186/2001-1326-1-29.
PMID: 23369283
citation: Kindrachuk J, Ork B, Hart BJ, Mazur S, Holbrook MR, Frieman MB, Traynor D, Johnson RF, Dyall J, Kuhn JH, Olinger GG, Hensley LE, Jahrling PB. Antiviral potential of ERK/MAPK and PI3K/AKT/mTOR signaling modulation for Middle East respiratory syndrome coronavirus infection as identified by temporal kinome analysis. Antimicrob Agents Chemother. 2015 Feb;59(2):1088-99. doi: 10.1128/AAC.03659-14. Epub 2014 Dec 8.
PMID: 25487801
citation: Wang CH, Chung FT, Lin SM, Huang SY, Chou CL, Lee KY, Lin TY, Kuo HP. Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure. Crit Care Med. 2014 Feb;42(2):313-21. doi: 10.1097/CCM.0b013e3182a2727d.
PMID: 24105455
citation: Jia X, Liu B, Bao L, Lv Q, Li F, Li H, An Y, Zhang X, Cao B, Wang C. Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration. PLoS Pathog. 2018 Nov 13;14(11):e1007428. doi: 10.1371/journal.ppat.1007428. eCollection 2018 Nov.
PMID: 30422993
citation: Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14. doi: 10.1038/s41421-020-0153-3. eCollection 2020.
PMID: 32194980
responsible party type: Principal Investigator
investigator affiliation: Alexandria University
investigator full name: Mohamed Mamdouh Mahmoud Mohamed Elsayed , MD
investigator title: lecturer
mesh term: COVID-19
mesh term: Sirolimus
sharing ipd: Undecided