<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/NCT04444271</url>
  </required_header>
  <id_info>
    <org_study_id>NIBMT-MSc-COVID-2020</org_study_id>
    <nct_id>NCT04444271</nct_id>
  </id_info>
  <brief_title>Mesenchymal Stem Cell Infusion for COVID-19 Infection</brief_title>
  <official_title>Prospective, Randomized Phase 2 Clinical Trial of Mesenchymal Stem Cells(MSCs) for the Treatment of Coronavirus Disease 2019(COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dr. Zaineb Akram</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Blood and Marrow Transplant (NIBMT), Pakistan</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have&#xD;
      carried out/published clinical trials on treatment based on Western medicine, traditional&#xD;
      Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used&#xD;
      antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There&#xD;
      are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins,&#xD;
      Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem&#xD;
      cells. However, most of these trials were small (median sample size 100) and the bulk of&#xD;
      potential therapeutic strategies remain in the experimental phase and currently there is no&#xD;
      eﬀective speciﬁc antiviral with high-level evidence.The aim of this study is assess the&#xD;
      efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with&#xD;
      moderate/severe COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      All patients will receive 2x10^6 cells/kg on days 1 and day 7 (if needed). The study will be&#xD;
      divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2&#xD;
      groups (5 Treatment arm; 5 Control Arm) and receive 2 x10^6 cells/kg MSCs on days 1 and 7 in&#xD;
      addition to standard care. Thereafter, the trial committee will meet and evaluate all&#xD;
      collected safety and efficacy information to decide about crossover of Control arm to&#xD;
      treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects&#xD;
      will be included in the study and treated according to protocol.&#xD;
&#xD;
      Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml&#xD;
      bone marrow will be collected from iliac crest using aseptic technique in syringes primed&#xD;
      with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS)&#xD;
      and MSCs will be separated using density gradient centrifugation. After resuspension the&#xD;
      cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed&#xD;
      flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every&#xD;
      third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the&#xD;
      cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic&#xD;
      acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for&#xD;
      future use or infused immediately.&#xD;
&#xD;
      Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by&#xD;
      multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious&#xD;
      Disease Specialist, Clinical Hematologist.&#xD;
&#xD;
        1. Demand for MSCs will be initiated on pre-designated forms , signed by Critical care&#xD;
           Specialist Clearly indicating indication of MSCs.&#xD;
&#xD;
        2. Request form will be sent Stem Cell Lab.&#xD;
&#xD;
        3. Incharge stem Cell Lab will authorize issuance of the MSCs dose.&#xD;
&#xD;
        4. Stem Cell Lab will issue the dose Administration of MSCs&#xD;
&#xD;
      1. Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use&#xD;
      and given intravenously. The patients should be pre-medicated to avoid allergic reactions to&#xD;
      third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be&#xD;
      administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on&#xD;
      supportive care&#xD;
&#xD;
      Proposed usage:&#xD;
&#xD;
      Because of the very limited availability of MSCs, their usage has to be rationalized by MDT&#xD;
      comprising of pulmonologist, critical care specialist and clinical haematologist and&#xD;
      Infectious disease specialist.There is not enough evidence to put forth therapeutic&#xD;
      recommendations however, treatment decisions can be made on case to case basis after MDT.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 1, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">August 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>30 days post intervention</time_frame>
    <description>Assessment of Overall survival at 30 days post intervention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement</measure>
    <time_frame>30 days</time_frame>
    <description>days required for oxygen support independence after intervention</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of COVID19 PCR negativity</measure>
    <time_frame>day 1,3,7,10, 14</time_frame>
    <description>PCR testing to check PCR negativity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological improvement (day 15 and day 30 assessment)</measure>
    <time_frame>day 15 and day30</time_frame>
    <description>Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>days required to discharge from hospital</measure>
    <time_frame>30 days post admission</time_frame>
    <description>number of days required for discharge from hospital</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Only supportive care will be given to 10 patients</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mesenchymal stem cells</intervention_name>
    <description>1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care</description>
    <arm_group_label>Mesenchymal stem cells</arm_group_label>
    <other_name>MSCs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>100 ml of normal saline will be given intravenously to control arm</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, aged ≥ 10years&#xD;
&#xD;
          2. Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain&#xD;
             reaction (RT-PCR) from any diagnostic sampling source; and&#xD;
&#xD;
          3. Moderate illness: In compliance with the 2019-coronavirus pneumonia diagnosis standard&#xD;
             [according to the novel coronavirus infection pneumonia diagnosis and treatment&#xD;
             program (Trial Implementation Version 6) issued by the National Health and Medical&#xD;
             Commission, and world health organization (WHO) 2019 new coronavirus guidelines&#xD;
             standards]: (A) increased breathing rate (≥30 beats / min), difficulty breathing,&#xD;
             cyanosis of the lips; (B) in resting state, means oxygen saturation ≤93%; (C) partial&#xD;
             pressure of arterial oxygen (PaO2) / Fraction of inspired oxygen (FiO2) ≤300 mmHg&#xD;
             (1mmHg = 0.133kPa);&#xD;
&#xD;
          4. Critically ill : Respiratory failure, Septic Shock, muti-organ dysfunction syndrome&#xD;
             (MODS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with systemic autoimmune diseases&#xD;
&#xD;
          2. Not consenting for clinical trial&#xD;
&#xD;
          3. Those declared not for resuscitation due to underlying comorbid or current critical&#xD;
             condition&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>xanab akram</last_name>
    <role>Study Chair</role>
    <affiliation>NIBMT</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>xanab akram</last_name>
    <phone>03325346564</phone>
    <email>xanab.akram@gmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>NIBMT</name>
      <address>
        <city>Rawalpindi</city>
        <state>Punjab</state>
        <zip>46000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xanab Akram</last_name>
      <phone>03325346564</phone>
    </contact>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>June 27, 2020</last_update_submitted>
  <last_update_submitted_qc>June 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>National Institute of Blood and Marrow Transplant (NIBMT), Pakistan</investigator_affiliation>
    <investigator_full_name>Dr. Zaineb Akram</investigator_full_name>
    <investigator_title>Research officer</investigator_title>
  </responsible_party>
  <keyword>Coronavirus</keyword>
  <keyword>Mesenchymal Stem Cells</keyword>
  <keyword>Survival</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04444271
org study id: NIBMT-MSc-COVID-2020
nct id: NCT04444271
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Since the outbreak of coronavirusdisease2019(COVID-19), many researchers in China have
      carried out/published clinical trials on treatment based on Western medicine, traditional
      Chinese medicine or a combination of the two. Trials on treatment modalities have mainly used
      antivirals, interferon, glucocorticoids in addition to traditional Chinese medicine. There
      are also clinical trials exploring hydroxyquinoline/chloroquine sulphate, immunoglobulins,
      Vitamin-C, washed microbiota, nebulized interferon, teicoplanin as well as Mesenchymal stem
      cells. However, most of these trials were small (median sample size 100) and the bulk of
      potential therapeutic strategies remain in the experimental phase and currently there is no
      eﬀective speciﬁc antiviral with high-level evidence.The aim of this study is assess the
      efficacy of MSCs as an add-on therapy to standard supportive treatment for patients with
      moderate/severe COVID-19.
All patients will receive 2x10^6 cells/kg on days 1 and day 7 (if needed). The study will be
      divided in 2 phases. In the first phase, 10 patients will be included and randomized to 2
      groups (5 Treatment arm; 5 Control Arm) and receive 2 x10^6 cells/kg MSCs on days 1 and 7 in
      addition to standard care. Thereafter, the trial committee will meet and evaluate all
      collected safety and efficacy information to decide about crossover of Control arm to
      treatment arm if patient deteriorates clinically while in Control arm. Then, 10 new subjects
      will be included in the study and treated according to protocol.

      Preparation of MSCs doses MSCs will be isolated from bone marrow harvested cells. About 50ml
      bone marrow will be collected from iliac crest using aseptic technique in syringes primed
      with anticoagulant. The collected sample will be diluted with Phosphate Buffer Saline (PBS)
      and MSCs will be separated using density gradient centrifugation. After resuspension the
      cells will be seeded at a fixed concentration of 100,000 cells/cm2 in specially designed
      flasks and incubated at 37oC in 5% carbondioxide (CO2). Medium will be changed after every
      third day till harvesting of MSCs from the flasks. Once confluent (approximately day 20) the
      cells will be harvested with sterile techniques using Trypsin- Ethylenediaminetetraacetic
      acid ( EDTA ) solution. The prepared cells can either be stored in 50ml cryogenic vials for
      future use or infused immediately.

      Patient Selection and MSCs demand Patient for MSCs and Control arm will be selected by
      multidisciplinary team (MDT) comprising Critical Care Specialist, Pulmonologist, Infectious
      Disease Specialist, Clinical Hematologist.

        1. Demand for MSCs will be initiated on pre-designated forms , signed by Critical care
           Specialist Clearly indicating indication of MSCs.

        2. Request form will be sent Stem Cell Lab.

        3. Incharge stem Cell Lab will authorize issuance of the MSCs dose.

        4. Stem Cell Lab will issue the dose Administration of MSCs

      1. Experimental arm: Frozen MSCs will be resuspended in 100ml normal saline for immediate use
      and given intravenously. The patients should be pre-medicated to avoid allergic reactions to
      third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be
      administered on day 1,7 in addition to supportive care 2. Control Arm: Will be Continued on
      supportive care

      Proposed usage:

      Because of the very limited availability of MSCs, their usage has to be rationalized by MDT
      comprising of pulmonologist, critical care specialist and clinical haematologist and
      Infectious disease specialist.There is not enough evidence to put forth therapeutic
      recommendations however, treatment decisions can be made on case to case basis after MDT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 30 days post intervention
description: Assessment of Overall survival at 30 days post intervention
measure: Clinical improvement
time frame: 30 days
description: days required for oxygen support independence after intervention
measure: Time of COVID19 PCR negativity
time frame: day 1,3,7,10, 14
description: PCR testing to check PCR negativity
measure: Radiological improvement (day 15 and day 30 assessment)
time frame: day 15 and day30
description: Computed tomography Chest assesment will be done to assess improvment in radiological findings of COVID-19
measure: days required to discharge from hospital
time frame: 30 days post admission
description: number of days required for discharge from hospital
arm group label: Mesenchymal stem cells
arm group type: Experimental
description: 10 patients will be given mesenchymal stem cells at dose 2x10^6 cells/kg MSCs on days 1 and day 7 (if needed) in addition to standard care
arm group label: Placebo
arm group type: Placebo Comparator
description: Only supportive care will be given to 10 patients
intervention type: Drug
intervention name: Mesenchymal stem cells
description: 1. Frozen MSCs will be resuspended in 100ml normal saline for immediate use and given intravenously. The patients should be pre-medicated to avoid allergic reactions to third party MSCs. Each patient in Experimental arm will be given 2 x 106 cells/kg will be administered on day 1,7 in addition to supportive care
arm group label: Mesenchymal stem cells
other name: MSCs
intervention type: Other
intervention name: Placebo
description: 100 ml of normal saline will be given intravenously to control arm
arm group label: Placebo
criteria: 
gender: All
minimum age: 10 Years
maximum age: N/A
healthy volunteers: No
last name: xanab akram
role: Study Chair
affiliation: NIBMT
last name: xanab akram
phone: 03325346564
email: xanab.akram@gmail.com
facility: 
status: Recruiting
contact: 
country: Pakistan
responsible party type: Sponsor-Investigator
investigator affiliation: National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
investigator full name: Dr. Zaineb Akram
investigator title: Research officer
mesh term: COVID-19
sharing ipd: No