<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/NCT04457349</url>
  </required_header>
  <id_info>
    <org_study_id>plasma exchange in COVID 19</org_study_id>
    <nct_id>NCT04457349</nct_id>
  </id_info>
  <brief_title>Therapeutic Plasma Exchange in Resistant Cytokine Storm of COVID 19</brief_title>
  <official_title>Does Therapeutic Plasma Exchange Have A Role in Resistant Cytokine Storm State Of 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 of Therapeutic Plasma Exchange (TPE)&#xD;
      treatment in COVID-19 patients with resistant cytokine storm state.&#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 (SARS-CoV-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 19June 2020, COVID-19 has been confirmed in 8,385,440&#xD;
      individuals globally with deaths reaching 450,686 with a morality of 5.37%. Egypt has 50,437&#xD;
      confirmed cases and 1938 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 are usually increased while procalcitonin levels are normal&#xD;
      and elevation of procalcitonin usually indicates secondary bacterial infection. Ferritin,&#xD;
      D-dimer, and creatine kinase elevation is associated with severe disease. Chest computed&#xD;
      tomographic scans show a typical pattern of bilateral patchy shadows or ground glass 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 IL-1, IL-6, IL-8,&#xD;
      IL-10, tumour necrosis factor α (TNF-α) and interferon Ȣ(IFN-Ȣ) stimulating immune cells to&#xD;
      invade sites of infection causing endothelial dysfunction, vascular damage, alveolar damage&#xD;
      and ARDS. Cytokine storm has been reported in several viral infections including influenza&#xD;
      H5N1 virus, influenza H1N1 virus, and the two coronaviruses highly related to COVID-19;&#xD;
      &quot;SARS-CoV&quot; and &quot;MERS-CoV&quot;.&#xD;
&#xD;
      Therapeutic approaches to manage the COVID-19 cytokine storm might provide an avenue to&#xD;
      decrease the COVID-19 associated morbidity and mortality. Options include immunomodulators,&#xD;
      cytokine antagonists and cytokine removal. Tocilizumab (IL-6 antagonist), Anakinra&#xD;
      (antagonist of IL-1 β), TNF blockers, ruxolitinib (JAK1/2 inhibitor ), corticosteroids,&#xD;
      intravenous immunoglobulins and therapeutic plasma exchange (TPE) have been used with&#xD;
      variable efficacy.&#xD;
&#xD;
      Therapeutic plasma exchange can remove inflammatory factors, block the &quot;cytokine storm&quot;, to&#xD;
      reduce the damage of inflammatory response to the body. This therapy can be used for severe&#xD;
      and critical patients in the early and middle stages of the disease. Patel and colleagues&#xD;
      utilized TPE during the 2009 H1N1 influenza A outbreak in three pediatric patients presenting&#xD;
      in a similar fashion to those seen with fulminant COVID-19 today. All three had full recovery&#xD;
      from their illness after receiving rescue TPE. Adeli at al. used TPE as a rescue therapy in&#xD;
      patients with severe forms of COVID-19 ( septic shock, ARDS ) with very good results. Out of&#xD;
      8 patients, 7 patients improved and one patient died. Zhang et al. also tried TPE in three&#xD;
      COVID-19 patients who despite receiving antiviral treatment developed respiratory distress&#xD;
      and levels of IL-6 increased rapidly. All patients improved clinically and radiologically&#xD;
      with negative nucleic acid testing and were discharged 10-14 days later.&#xD;
&#xD;
      In Egypt, the first line drug to treat cytokine storm of COVID-19 is tocilizumab with good&#xD;
      results. But a considerable percentage of patients do not respond to it leaving physicians&#xD;
      with very limited options and usually patients deteriorated rapidly with high mortality.&#xD;
      Based on the encouraging results of TPE in severe COVID-19 infections and the familiarity of&#xD;
      the procedure, TPE could be a good option in those patients who do not respond to&#xD;
      tocilizumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 25, 2020</start_date>
  <completion_date type="Actual">January 20, 2021</completion_date>
  <primary_completion_date type="Actual">December 29, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>mortality</measure>
    <time_frame>28 day</time_frame>
    <description>Number of patients deaths of the total of patients included</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>the mean time with oxygen therapy</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>to calculate the mean time with oxygen therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the mean time with Non-invasive mechanical ventilation</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>to calculate the mean time with Non-invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the mean time of intubation</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>to calculate the mean time of intubation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>respiratory function parameters</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To calculate the mean of PaO2/FiO2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>respiratory function parameters</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To calculate the mean of levels of oxygen saturation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>radiological lung extension</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>to evaluate the lung extension of pneumonia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mean duration of hospitalization and ICU use</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>Days of hospitalization in survivors and/or days at ICU throughout the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the requirement of additional organ support</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>Percentage of patients with dialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the levels of IL-6</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the effect of TPE on the serum levels of inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To calculate the number of adverse events in patients with COVID-19 treated with TPE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the time to RT-PCR virus negativity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the levels of CRP</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the effect of TPE on the serum levels of inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the levels of procalcitonin (PCT)</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the effect of TPE on the serum levels of inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of D-dimer</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the effect of TPE on the serum levels of inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>levels of ferritin</measure>
    <time_frame>through study completion, and average of 1 month</time_frame>
    <description>To evaluate the effect of TPE on the serum levels of inflammatory markers</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>Therapeutic Plasma Exchange (TPE)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient will undergo two sessions. TPE will be done through filtration technique using a plasma filter at a dose of (1-1.5) plasma volume/session. Fresh frozen plasma or albumin 5% will be used to replace plasma.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Therapeutic Plasma Exchange (TPE)</intervention_name>
    <description>Treatment with Therapeutic Plasma Exchange (TPE)</description>
    <arm_group_label>Therapeutic Plasma Exchange (TPE)</arm_group_label>
    <other_name>plasmapheresis</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COVID-19 positive patients (confirmed by PCR) with cytokine storm state who will not&#xD;
             improve after two doses of tocilizumab.&#xD;
&#xD;
               -  Criteria of failure (resistance) to tocilizumab:&#xD;
&#xD;
                    1. Persistent high IL-6 and CRP.&#xD;
&#xD;
                    2. Persistent worsening of respiratory symptoms ( dyspnea, tachypnea, increased&#xD;
                       oxygen (O2) requirements or even need for mechanical ventilation).&#xD;
&#xD;
                    3. Partial arterial pressure of oxygen to fractional inspired concentration of&#xD;
                       oxygen (PaO2/FiO2) ratio &lt; 150.&#xD;
&#xD;
                    4. Persistent fever (˃38.5°C) despite normal procalcitonin level.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refractory septic shock:&#xD;
&#xD;
        ( It is defined according to surviving sepsis campaign as the presence of hypotension with&#xD;
        end organ dysfunction requiring high dose vasopressor support often greater than 0.5&#xD;
        µg/kg/min norepinephrine or equivalent).&#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 of Nephrology &amp; Internal Medicine, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>montasser M zeid, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor of Nephrology &amp; Internal Medicine, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Akram M Fayed, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor of Critical Care Medicine, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ehab M El Reweny, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistant Professor of Critical Care Medicine, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nermine H Zakaria, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Professor of Clinical and Chemical Pathology Medicine, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ayman I Baess, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Assistant Professor of Chest Diseases, Faculty of Medicine, Alexandria university, Egypt</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Faculty of Medicine, Alexandria university, Egypt</name>
      <address>
        <city>Alexandria</city>
        <zip>21526</zip>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Egypt</country>
  </location_countries>
  <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>Kalaiyarasu S, Kumar M, Senthil Kumar D, Bhatia S, Dash SK, Bhat S, Khetan RK, Nagarajan S. Highly pathogenic avian influenza H5N1 virus induces cytokine dysregulation with suppressed maturation of chicken monocyte-derived dendritic cells. Microbiol Immunol. 2016 Oct;60(10):687-693. doi: 10.1111/1348-0421.12443.</citation>
    <PMID>27730669</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>Ye Q, Wang B, Mao J. The pathogenesis and treatment of the ;Cytokine Storm' in COVID-19. J Infect. 2020 Jun;80(6):607-613. doi: 10.1016/j.jinf.2020.03.037. Epub 2020 Apr 10.</citation>
    <PMID>32283152</PMID>
  </reference>
  <reference>
    <citation>Patel P, Nandwani V, Vanchiere J, Conrad SA, Scott LK. Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A--an associated respiratory failure and hemodynamic shock. Pediatr Crit Care Med. 2011 Mar;12(2):e87-9. doi: 10.1097/PCC.0b013e3181e2a569.</citation>
    <PMID>20453703</PMID>
  </reference>
  <reference>
    <citation>Adeli SH, Asghari A, Tabarraii R, Shajari R, Afshari S, Kalhor N, Vafaeimanesh J. Therapeutic plasma exchange as a rescue therapy in patients with coronavirus disease 2019: a case series. Pol Arch Intern Med. 2020 May 29;130(5):455-458. doi: 10.20452/pamw.15340. Epub 2020 May 7. No abstract available.</citation>
    <PMID>32380821</PMID>
  </reference>
  <reference>
    <citation>Zhang L, Zhai H, Ma S, Chen J, Gao Y. Efficacy of therapeutic plasma exchange in severe COVID-19 patients. Br J Haematol. 2020 Aug;190(4):e181-e183. doi: 10.1111/bjh.16890. Epub 2020 Jun 12. No abstract available.</citation>
    <PMID>32453903</PMID>
  </reference>
  <reference>
    <citation>Bassi E, Park M, Azevedo LC. Therapeutic strategies for high-dose vasopressor-dependent shock. Crit Care Res Pract. 2013;2013:654708. doi: 10.1155/2013/654708. Epub 2013 Sep 15.</citation>
    <PMID>24151551</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>April 13, 2022</last_update_submitted>
  <last_update_submitted_qc>April 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 15, 2022</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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Cytokine Release Syndrome</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04457349
org study id: plasma exchange in COVID 19
nct id: NCT04457349
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This research is planned to illustrate the efficacy of Therapeutic Plasma Exchange (TPE)
      treatment in COVID-19 patients with resistant cytokine storm state.
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 (SARS-CoV-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 19June 2020, COVID-19 has been confirmed in 8,385,440
      individuals globally with deaths reaching 450,686 with a morality of 5.37%. Egypt has 50,437
      confirmed cases and 1938 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 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 IL-1, IL-6, IL-8,
      IL-10, tumour necrosis factor α (TNF-α) and interferon Ȣ(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 "MERS-CoV".

      Therapeutic approaches to manage the COVID-19 cytokine storm might provide an avenue to
      decrease the COVID-19 associated morbidity and mortality. Options include immunomodulators,
      cytokine antagonists and cytokine removal. Tocilizumab (IL-6 antagonist), Anakinra
      (antagonist of IL-1 β), TNF blockers, ruxolitinib (JAK1/2 inhibitor ), corticosteroids,
      intravenous immunoglobulins and therapeutic plasma exchange (TPE) have been used with
      variable efficacy.

      Therapeutic plasma exchange can remove inflammatory factors, block the "cytokine storm", to
      reduce the damage of inflammatory response to the body. This therapy can be used for severe
      and critical patients in the early and middle stages of the disease. Patel and colleagues
      utilized TPE during the 2009 H1N1 influenza A outbreak in three pediatric patients presenting
      in a similar fashion to those seen with fulminant COVID-19 today. All three had full recovery
      from their illness after receiving rescue TPE. Adeli at al. used TPE as a rescue therapy in
      patients with severe forms of COVID-19 ( septic shock, ARDS ) with very good results. Out of
      8 patients, 7 patients improved and one patient died. Zhang et al. also tried TPE in three
      COVID-19 patients who despite receiving antiviral treatment developed respiratory distress
      and levels of IL-6 increased rapidly. All patients improved clinically and radiologically
      with negative nucleic acid testing and were discharged 10-14 days later.

      In Egypt, the first line drug to treat cytokine storm of COVID-19 is tocilizumab with good
      results. But a considerable percentage of patients do not respond to it leaving physicians
      with very limited options and usually patients deteriorated rapidly with high mortality.
      Based on the encouraging results of TPE in severe COVID-19 infections and the familiarity of
      the procedure, TPE could be a good option in those patients who do not respond to
      tocilizumab.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: mortality
time frame: 28 day
description: Number of patients deaths of the total of patients included
measure: the mean time with oxygen therapy
time frame: through study completion, and average of 1 month
description: to calculate the mean time with oxygen therapy
measure: the mean time with Non-invasive mechanical ventilation
time frame: through study completion, and average of 1 month
description: to calculate the mean time with Non-invasive mechanical ventilation
measure: the mean time of intubation
time frame: through study completion, and average of 1 month
description: to calculate the mean time of intubation
measure: respiratory function parameters
time frame: through study completion, and average of 1 month
description: To calculate the mean of PaO2/FiO2
measure: respiratory function parameters
time frame: through study completion, and average of 1 month
description: To calculate the mean of levels of oxygen saturation
measure: radiological lung extension
time frame: through study completion, and average of 1 month
description: to evaluate the lung extension of pneumonia
measure: mean duration of hospitalization and ICU use
time frame: through study completion, and average of 1 month
description: Days of hospitalization in survivors and/or days at ICU throughout the study
measure: the requirement of additional organ support
time frame: through study completion, and average of 1 month
description: Percentage of patients with dialysis
measure: the levels of IL-6
time frame: through study completion, and average of 1 month
description: To evaluate the effect of TPE on the serum levels of inflammatory markers
measure: Incidence of adverse events
time frame: through study completion, and average of 1 month
description: To calculate the number of adverse events in patients with COVID-19 treated with TPE
measure: time to reverse-transcriptase polymerase chain reaction (RT-PCR) virus negativity
time frame: through study completion, and average of 1 month
description: To evaluate the time to RT-PCR virus negativity
measure: the levels of CRP
time frame: through study completion, and average of 1 month
description: To evaluate the effect of TPE on the serum levels of inflammatory markers
measure: the levels of procalcitonin (PCT)
time frame: through study completion, and average of 1 month
description: To evaluate the effect of TPE on the serum levels of inflammatory markers
measure: levels of D-dimer
time frame: through study completion, and average of 1 month
description: To evaluate the effect of TPE on the serum levels of inflammatory markers
measure: levels of ferritin
time frame: through study completion, and average of 1 month
description: To evaluate the effect of TPE on the serum levels of inflammatory markers
arm group label: Therapeutic Plasma Exchange (TPE)
arm group type: Experimental
description: Each patient will undergo two sessions. TPE will be done through filtration technique using a plasma filter at a dose of (1-1.5) plasma volume/session. Fresh frozen plasma or albumin 5% will be used to replace plasma.
intervention type: Procedure
intervention name: Therapeutic Plasma Exchange (TPE)
description: Treatment with Therapeutic Plasma Exchange (TPE)
arm group label: Therapeutic Plasma Exchange (TPE)
other name: plasmapheresis
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 of Nephrology & Internal Medicine, Faculty of Medicine, Alexandria university, Egypt
last name: montasser M zeid, MD
role: Study Chair
affiliation: Professor of Nephrology & Internal Medicine, Faculty of Medicine, Alexandria university, Egypt
last name: Akram M Fayed, MD
role: Study Chair
affiliation: Professor of Critical Care Medicine, Faculty of Medicine, Alexandria university, Egypt
last name: Ehab M El Reweny, MD
role: Study Chair
affiliation: Assistant Professor of Critical Care Medicine, Faculty of Medicine, Alexandria university, Egypt
last name: Nermine H Zakaria, MD
role: Study Chair
affiliation: Professor of Clinical and Chemical Pathology Medicine, Faculty of Medicine, Alexandria university, Egypt
last name: Ayman I Baess, MD
role: Study Chair
affiliation: Assistant Professor of Chest Diseases, Faculty of Medicine, Alexandria university, Egypt
facility: 
country: Egypt
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PMID: 24151551
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: Cytokine Release Syndrome