<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/NCT04485169</url>
  </required_header>
  <id_info>
    <org_study_id>Sultan Mehmood Kamran</org_study_id>
    <nct_id>NCT04485169</nct_id>
  </id_info>
  <brief_title>Therapeutic Plasma Exchange for Coronavirus Disease-2019 Triggered Cytokine Release Storm;</brief_title>
  <acronym>Plex</acronym>
  <official_title>Therapeutic Plasma Exchange for Coronavirus Disease-2019 Triggered Cytokine Release Storm; a Retrospective Propensity Matched Control Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>UNICEF</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pak Emirates Military Hospital Rawalpindi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>UNICEF</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>
      Background:&#xD;
&#xD;
      investigators have seen recently from experience in Western countries with best health care&#xD;
      systems that pandemics cannot be managed in hospitals. Investigators have seen ICUs crowded&#xD;
      to capacity, healthcare workers being exposed and going to quarantine or dying after exposure&#xD;
      to large doses of viral inoculums. Investigators recommend that institutions should register&#xD;
      for Clinical trials and consider emergency use of TPE. In Pandemics, time is of essence to&#xD;
      avoid mortality by intervening early with available evidence, preferably as part of clinical&#xD;
      trial.&#xD;
&#xD;
      Scientific rationale:&#xD;
&#xD;
      Beyond supportive care, there are currently no proven treatment options for coronavirus&#xD;
      disease (COVID-19) and related pneumonia, caused by Severe Acute Respiratory Syndrome&#xD;
      Coronavirus 2 (SARS-CoV-2). However, literature review has shown that most common cause of&#xD;
      death in severe SARS-COV-2 is Cytokine release syndrome and Hemophygocytic Lymphohistocytosis&#xD;
      (HLH). In this context, Investigators seek to treat patients who are sick enough to warrant&#xD;
      hospitalization prior to the onset of overwhelming disease including a systemic inflammatory&#xD;
      response, sepsis, and/or Acute Respiratory Distress Syndrome (ARDS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PROTOCOL SUMMARY:&#xD;
&#xD;
      Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release storm; a&#xD;
      retrospective propensity matched control study&#xD;
&#xD;
      Clinical Phase: Two arms, Phase 2 Open Label&#xD;
&#xD;
      Conducted by: Department of Pulmonology and Critical Care; Pak Emirates Military Hospital.&#xD;
&#xD;
      Sample Size: 280&#xD;
&#xD;
      Study Population: Hospitalized COVID-19 patients aged ≥18 years to 80 years of with Moderate-&#xD;
      severe-critical disease and evidence of Cytokine release storm (CRS)&#xD;
&#xD;
      Study Duration: 1st April, 2020 to 31st July 2020&#xD;
&#xD;
      Study Design: A retrospective propensity matched control trial will assess the efficacy and&#xD;
      safety of following treatment options&#xD;
&#xD;
        1. Standard treatment including steroids&#xD;
&#xD;
        2. Therapeutic plasma exchange in addition to standard treatment&#xD;
&#xD;
      Operational Definitions&#xD;
&#xD;
        1. Moderate disease:&#xD;
&#xD;
           COVID-19 positive case with lung infiltrates &lt; 50% of total lung fields on Chest X-ray /&#xD;
           peripheral ground glass opacities (GGOs) on High Resolution Computerized Tomography&#xD;
           (HRCT)chest but no evidence of hypoxemia.&#xD;
&#xD;
        2. Severe disease:&#xD;
&#xD;
           COVID-19 pneumonia with evidence of hypoxemia (RR &gt; 30/minute or PaO2 on ABGs &lt; 80mmHg&#xD;
           or PaO2/FiO2 (PF ratio) &lt; 300 or lung infiltrates &gt; 50% of the lung field).&#xD;
&#xD;
        3. Critical illness:&#xD;
&#xD;
           COVID-19 pneumonia with evidence of either respiratory failure (PaO2 &lt; 60mmHg) or&#xD;
           multiorgan dysfunction syndrome (MODS) measured by Sequential Organ Failure assessment&#xD;
           (SOFA score) &gt; 10 or septic shock (Systolic BP less than 90 or less than 40mm Hg of&#xD;
           baseline in hypertensive or Urine output &lt; 0.5 ml/kg/hour).Age, sex, comorbidities, date&#xD;
           of symptoms, source of infection, type of admission SOFA score, Clinical status, vital&#xD;
           signs including temperature, respiratory rate, oxygen saturation, oxygen requirement,&#xD;
           Complete Blood counts (CBC) with neutrophil counts, lymphocytes count, C-reactive&#xD;
           Proteins (CRP), chest imaging (CT or X-ray), location and status in hospital&#xD;
&#xD;
        4. Cytokine release storm (CRS):&#xD;
&#xD;
      Diagnostic criteria of Cytokine release syndrome (CRS) CRS is defined as fever of equal to or&#xD;
      more than 100 F persisting &gt; 48 hours in absence of documented bacterial infection and ANY of&#xD;
      the following in the presence of moderate, severe or critical disease&#xD;
&#xD;
        1. Ferritin &gt;1000 mcg/L and rising in last 24 hours&#xD;
&#xD;
        2. Ferritin &gt;2000 mcg/L in patient requiring high flow oxygen or ventilation&#xD;
&#xD;
        3. Lymphopenia &lt; 800 cells/ul or lymphocyte percentage &lt;20% and two of the following&#xD;
&#xD;
             1. Ferritin &gt;700 mcg/mL and rising in the last 24 hours&#xD;
&#xD;
             2. LDH &gt; 300 IU (reference 140-250 IU/L) and rising in the last 24 hours&#xD;
&#xD;
             3. D-Dimer &gt;1000ng/mL (or &gt;1mcg/ml) and rising in the last 24 hours&#xD;
&#xD;
             4. CRP &gt;70 mg/L (or &gt;10 hsCRP) and rising in the last 24 hours, in absence of&#xD;
                bacterial infection&#xD;
&#xD;
             5. If any 3 of above presents on admission no need to document rise&#xD;
&#xD;
      5. Standard treatment:&#xD;
&#xD;
      As per Institutional COVID-19 Management Guidelines all patients of moderate, severe and&#xD;
      critical COVID-19 received standard protocol of aspirin, anticoagulation, ulcer prophylaxis,&#xD;
      awake Proning (if PaO2 &lt; 80mmHg) and corticosteroids. All patients of CRS received&#xD;
      Methylprednisolone 1 mg/kg irrespective of disease severity.&#xD;
&#xD;
      6. Therapeutic Plasma exchange (TPE)&#xD;
&#xD;
      Therapeutic plasma exchange: 1-1.5 plasma exchange daily (1-5 sessions) with replacement&#xD;
      fluid Fresh frozen Plasma (FFP) (whole volume) to 70 willing patients of moderate, severe and&#xD;
      critical disease with evidence of CRS after explaining the investigational role of this&#xD;
      therapy. TPE will be given in addition to standard treatment to 70 patients randomly. TPE&#xD;
      related complications to be documented&#xD;
&#xD;
      7. Recovery Recovery to be defined by de-escalation of patients condition from severe to&#xD;
      moderate, or from moderate to mild, plus at least 2 of the following; serum Ferritin &lt; 1000&#xD;
      ug/ml (and decreasing trend on two consecutive days), serum LDH normalization, C-reactive&#xD;
      protein &gt; 50% fold reduction (and decreasing trend in on two consecutive days),), ALC &gt; 1000&#xD;
      and PT/APTT normalization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2020</start_date>
  <completion_date type="Actual">July 31, 2020</completion_date>
  <primary_completion_date type="Actual">July 31, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>It was an interventional retrospective Propensity score matched (PSM) single centre based cohort study in Pak Emirates Military Hospital Rawalpindi (PEMH), Pakistan from 1st April to 30th June 2020. This study was carried out at the Department of Pulmonology and Critical care. PEMH is the largest Covid-19 designated hospital in the country. Data of all hospitalized patients is maintained by PEMH Covid-19 Research and evaluation cell. The study was approved by Institutional Review Board.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>28 days</time_frame>
    <description>Death or recovery</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospitalization</measure>
    <time_frame>28 days</time_frame>
    <description>Duration of hospitalization in days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Timing of PCR negativity</measure>
    <time_frame>28 days</time_frame>
    <description>Time in days to achieve viral clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to CRS resolution</measure>
    <time_frame>28 days</time_frame>
    <description>Time in days required to settle symptoms and laboratory parameters of CRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Complications</measure>
    <time_frame>28 days</time_frame>
    <description>Complications secondary to use of TPE</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">280</enrollment>
  <condition>COVID-19</condition>
  <condition>Cytokine Release Syndrome</condition>
  <arm_group>
    <arm_group_label>TPE Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In addition to standard care TPE was performed once daily using COBE Spectra Apheresis machine version 7 (Manufacturer TERUMO BCT, Lakewood, CO, USA INC) having continuous flow centrifugation. Venous access was achieved using an ultrasound guided double lumen catheter (Arrow - 12 FR) via femoral vein. Patient's total blood volume was calculated as per Nadler's formula. Anticoagulant acid dextrose ratio was 1:10 and flow rate 30-40 ml/minutes (Adjusted as per hemodynamic status). Patients' blood pressure, pulse, oxygen saturation was monitored throughout procedure. Duration of procedure varied from 2-4 hours and 1-1.5 times total plasma volume was removed during each procedure. Replacement fluid was fresh frozen plasma (FFP) and normal saline in 2:1 respectively. All procedures were performed in intensive care or high dependency unit by Apheresis Department of PEMH. TPE was continued till recovery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NON TPE arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Only supportive treatment offered including Vit C, Zinc, Vit D, famotidine, Enoxaparin and Methylprednisolone</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Therapeutic Plasma Exchange</intervention_name>
    <description>a. 1-1.5 plasma volume exchange, 2/3rd plasma should be replacing with FFP to avoid coagulopathy, adequate dieresis to prevent volume overload, 1-5 sessions in total, 1 session daily</description>
    <arm_group_label>TPE Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  COVID-19 diagnosed by Polymerase Chain Reaction (PCR) positivity for SARS-CoV2&#xD;
&#xD;
          -  CRS at presentation or developing during hospitalization&#xD;
&#xD;
          -  10-80 years age and both genders&#xD;
&#xD;
          -  hospital admission&#xD;
&#xD;
          -  At least 1 completed session of plasma-exchange in patients included in TPE arm&#xD;
&#xD;
          -  No other novel therapy administered.&#xD;
&#xD;
        Exclusion criteria were:&#xD;
&#xD;
          -  Death within 48 hours of admission&#xD;
&#xD;
          -  severe septic shock at time of admission&#xD;
&#xD;
          -  Congestive cardiac failure (EF&lt;20%) (4)&#xD;
&#xD;
          -  Those receiving immunotherapy, Anti-thymocyte globulin or hematopoietic stem cell&#xD;
             transplant in recent past&#xD;
&#xD;
          -  Patients of hematological or solid organ malignancies&#xD;
&#xD;
          -  patients receiving other investigational drugs including Tocilizumab, Convalescent&#xD;
             plasma, Remdesivir, or Mesenchymal stem cells.&#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>Imran m Fazal, FCPS</last_name>
    <role>Study Director</role>
    <affiliation>Pak Emirates Military Hospital (PEMH) Rawalpindi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pak Emirates Military Hospital</name>
      <address>
        <city>Rawalpindi</city>
        <state>Punjab</state>
        <zip>46000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>6. Clinical Management Guidelines for COVID-19 Infections, Version 2 [Internet]. Nhsrc.gov.pk. 2020 [cited 1 July 2020]. Available from: http://www.nhsrc.gov.pk/SiteImage/Misc/files/Clinical-Management-nfection%20v2.pdf</citation>
  </reference>
  <reference>
    <citation>Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, Pham HP, Schneiderman J, Witt V, Wu Y, Zantek ND, Dunbar NM, Schwartz GEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019 Jun;34(3):171-354. doi: 10.1002/jca.21705.</citation>
    <PMID>31180581</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>Busund R, Koukline V, Utrobin U, Nedashkovsky E. Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial. Intensive Care Med. 2002 Oct;28(10):1434-9. doi: 10.1007/s00134-002-1410-7. Epub 2002 Jul 23.</citation>
    <PMID>12373468</PMID>
  </reference>
  <reference>
    <citation>Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020 Apr 2;24(1):128. doi: 10.1186/s13054-020-2836-4. No abstract available.</citation>
    <PMID>32241301</PMID>
  </reference>
  <reference>
    <citation>Shi H, Zhou C, He P, Huang S, Duan Y, Wang X, Lin K, Zhou C, Zhang X, Zha Y. Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with COVID-19. Int J Antimicrob Agents. 2020 Aug;56(2):105974. doi: 10.1016/j.ijantimicag.2020.105974. Epub 2020 Apr 13.</citation>
    <PMID>32298745</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>Ma J, Xia P, Zhou Y, Liu Z, Zhou X, Wang J, Li T, Yan X, Chen L, Zhang S, Qin Y, Li X. Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19. Clin Immunol. 2020 May;214:108408. doi: 10.1016/j.clim.2020.108408. Epub 2020 Apr 1. No abstract available.</citation>
    <PMID>32247038</PMID>
  </reference>
  <results_reference>
    <citation>Knaup H, Stahl K, Schmidt BMW, Idowu TO, Busch M, Wiesner O, Welte T, Haller H, Kielstein JT, Hoeper MM, David S. Early therapeutic plasma exchange in septic shock: a prospective open-label nonrandomized pilot study focusing on safety, hemodynamics, vascular barrier function, and biologic markers. Crit Care. 2018 Oct 30;22(1):285. doi: 10.1186/s13054-018-2220-9.</citation>
    <PMID>30373638</PMID>
  </results_reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>September 24, 2020</last_update_submitted>
  <last_update_submitted_qc>September 24, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>UNICEF</investigator_affiliation>
    <investigator_full_name>sultan mehmood kamran</investigator_full_name>
    <investigator_title>Classified Medical specialist</investigator_title>
  </responsible_party>
  <keyword>Therapeutic Plasma exchange</keyword>
  <keyword>Cytokine release storm</keyword>
  <keyword>COVID-19</keyword>
  <keyword>ARDS</keyword>
  <keyword>Critical disease</keyword>
  <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>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>data can be shared on demand in SPSS sheet</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>Data is available right now and will remain available (6 months)</ipd_time_frame>
    <ipd_access_criteria>By email</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/NCT04485169
org study id: Sultan Mehmood Kamran
nct id: NCT04485169
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Background:

      investigators have seen recently from experience in Western countries with best health care
      systems that pandemics cannot be managed in hospitals. Investigators have seen ICUs crowded
      to capacity, healthcare workers being exposed and going to quarantine or dying after exposure
      to large doses of viral inoculums. Investigators recommend that institutions should register
      for Clinical trials and consider emergency use of TPE. In Pandemics, time is of essence to
      avoid mortality by intervening early with available evidence, preferably as part of clinical
      trial.

      Scientific rationale:

      Beyond supportive care, there are currently no proven treatment options for coronavirus
      disease (COVID-19) and related pneumonia, caused by Severe Acute Respiratory Syndrome
      Coronavirus 2 (SARS-CoV-2). However, literature review has shown that most common cause of
      death in severe SARS-COV-2 is Cytokine release syndrome and Hemophygocytic Lymphohistocytosis
      (HLH). In this context, Investigators seek to treat patients who are sick enough to warrant
      hospitalization prior to the onset of overwhelming disease including a systemic inflammatory
      response, sepsis, and/or Acute Respiratory Distress Syndrome (ARDS).
PROTOCOL SUMMARY:

      Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release storm; a
      retrospective propensity matched control study

      Clinical Phase: Two arms, Phase 2 Open Label

      Conducted by: Department of Pulmonology and Critical Care; Pak Emirates Military Hospital.

      Sample Size: 280

      Study Population: Hospitalized COVID-19 patients aged ≥18 years to 80 years of with Moderate-
      severe-critical disease and evidence of Cytokine release storm (CRS)

      Study Duration: 1st April, 2020 to 31st July 2020

      Study Design: A retrospective propensity matched control trial will assess the efficacy and
      safety of following treatment options

        1. Standard treatment including steroids

        2. Therapeutic plasma exchange in addition to standard treatment

      Operational Definitions

        1. Moderate disease:

           COVID-19 positive case with lung infiltrates < 50% of total lung fields on Chest X-ray /
           peripheral ground glass opacities (GGOs) on High Resolution Computerized Tomography
           (HRCT)chest but no evidence of hypoxemia.

        2. Severe disease:

           COVID-19 pneumonia with evidence of hypoxemia (RR > 30/minute or PaO2 on ABGs < 80mmHg
           or PaO2/FiO2 (PF ratio) < 300 or lung infiltrates > 50% of the lung field).

        3. Critical illness:

           COVID-19 pneumonia with evidence of either respiratory failure (PaO2 < 60mmHg) or
           multiorgan dysfunction syndrome (MODS) measured by Sequential Organ Failure assessment
           (SOFA score) > 10 or septic shock (Systolic BP less than 90 or less than 40mm Hg of
           baseline in hypertensive or Urine output < 0.5 ml/kg/hour).Age, sex, comorbidities, date
           of symptoms, source of infection, type of admission SOFA score, Clinical status, vital
           signs including temperature, respiratory rate, oxygen saturation, oxygen requirement,
           Complete Blood counts (CBC) with neutrophil counts, lymphocytes count, C-reactive
           Proteins (CRP), chest imaging (CT or X-ray), location and status in hospital

        4. Cytokine release storm (CRS):

      Diagnostic criteria of Cytokine release syndrome (CRS) CRS is defined as fever of equal to or
      more than 100 F persisting > 48 hours in absence of documented bacterial infection and ANY of
      the following in the presence of moderate, severe or critical disease

        1. Ferritin >1000 mcg/L and rising in last 24 hours

        2. Ferritin >2000 mcg/L in patient requiring high flow oxygen or ventilation

        3. Lymphopenia < 800 cells/ul or lymphocyte percentage <20% and two of the following

             1. Ferritin >700 mcg/mL and rising in the last 24 hours

             2. LDH > 300 IU (reference 140-250 IU/L) and rising in the last 24 hours

             3. D-Dimer >1000ng/mL (or >1mcg/ml) and rising in the last 24 hours

             4. CRP >70 mg/L (or >10 hsCRP) and rising in the last 24 hours, in absence of
                bacterial infection

             5. If any 3 of above presents on admission no need to document rise

      5. Standard treatment:

      As per Institutional COVID-19 Management Guidelines all patients of moderate, severe and
      critical COVID-19 received standard protocol of aspirin, anticoagulation, ulcer prophylaxis,
      awake Proning (if PaO2 < 80mmHg) and corticosteroids. All patients of CRS received
      Methylprednisolone 1 mg/kg irrespective of disease severity.

      6. Therapeutic Plasma exchange (TPE)

      Therapeutic plasma exchange: 1-1.5 plasma exchange daily (1-5 sessions) with replacement
      fluid Fresh frozen Plasma (FFP) (whole volume) to 70 willing patients of moderate, severe and
      critical disease with evidence of CRS after explaining the investigational role of this
      therapy. TPE will be given in addition to standard treatment to 70 patients randomly. TPE
      related complications to be documented

      7. Recovery Recovery to be defined by de-escalation of patients condition from severe to
      moderate, or from moderate to mild, plus at least 2 of the following; serum Ferritin < 1000
      ug/ml (and decreasing trend on two consecutive days), serum LDH normalization, C-reactive
      protein > 50% fold reduction (and decreasing trend in on two consecutive days),), ALC > 1000
      and PT/APTT normalization.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: It was an interventional retrospective Propensity score matched (PSM) single centre based cohort study in Pak Emirates Military Hospital Rawalpindi (PEMH), Pakistan from 1st April to 30th June 2020. This study was carried out at the Department of Pulmonology and Critical care. PEMH is the largest Covid-19 designated hospital in the country. Data of all hospitalized patients is maintained by PEMH Covid-19 Research and evaluation cell. The study was approved by Institutional Review Board.
primary purpose: Treatment
masking: None (Open Label)
measure: Survival
time frame: 28 days
description: Death or recovery
measure: Duration of Hospitalization
time frame: 28 days
description: Duration of hospitalization in days
measure: Timing of PCR negativity
time frame: 28 days
description: Time in days to achieve viral clearance
measure: Time to CRS resolution
time frame: 28 days
description: Time in days required to settle symptoms and laboratory parameters of CRS
measure: Complications
time frame: 28 days
description: Complications secondary to use of TPE
arm group label: TPE Arm
arm group type: Experimental
description: In addition to standard care TPE was performed once daily using COBE Spectra Apheresis machine version 7 (Manufacturer TERUMO BCT, Lakewood, CO, USA INC) having continuous flow centrifugation. Venous access was achieved using an ultrasound guided double lumen catheter (Arrow - 12 FR) via femoral vein. Patient's total blood volume was calculated as per Nadler's formula. Anticoagulant acid dextrose ratio was 1:10 and flow rate 30-40 ml/minutes (Adjusted as per hemodynamic status). Patients' blood pressure, pulse, oxygen saturation was monitored throughout procedure. Duration of procedure varied from 2-4 hours and 1-1.5 times total plasma volume was removed during each procedure. Replacement fluid was fresh frozen plasma (FFP) and normal saline in 2:1 respectively. All procedures were performed in intensive care or high dependency unit by Apheresis Department of PEMH. TPE was continued till recovery
arm group label: NON TPE arm
arm group type: No Intervention
description: Only supportive treatment offered including Vit C, Zinc, Vit D, famotidine, Enoxaparin and Methylprednisolone
intervention type: Procedure
intervention name: Therapeutic Plasma Exchange
description: a. 1-1.5 plasma volume exchange, 2/3rd plasma should be replacing with FFP to avoid coagulopathy, adequate dieresis to prevent volume overload, 1-5 sessions in total, 1 session daily
arm group label: TPE Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Imran m Fazal, FCPS
role: Study Director
affiliation: Pak Emirates Military Hospital (PEMH) Rawalpindi
facility: 
country: Pakistan
citation: 6. Clinical Management Guidelines for COVID-19 Infections, Version 2 [Internet]. Nhsrc.gov.pk. 2020 [cited 1 July 2020]. Available from: http://www.nhsrc.gov.pk/SiteImage/Misc/files/Clinical-Management-nfection%20v2.pdf
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PMID: 31180581
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PMID: 20453703
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PMID: 12373468
citation: Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020 Apr 2;24(1):128. doi: 10.1186/s13054-020-2836-4. No abstract available.
PMID: 32241301
citation: Shi H, Zhou C, He P, Huang S, Duan Y, Wang X, Lin K, Zhou C, Zhang X, Zha Y. Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with COVID-19. Int J Antimicrob Agents. 2020 Aug;56(2):105974. doi: 10.1016/j.ijantimicag.2020.105974. Epub 2020 Apr 13.
PMID: 32298745
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PMID: 32453903
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PMID: 32247038
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PMID: 30373638
responsible party type: Principal Investigator
investigator affiliation: UNICEF
investigator full name: sultan mehmood kamran
investigator title: Classified Medical specialist
mesh term: COVID-19
mesh term: Cytokine Release Syndrome
sharing ipd: Yes
ipd description: data can be shared on demand in SPSS sheet
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd time frame: Data is available right now and will remain available (6 months)
ipd access criteria: By email