<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/NCT04420364</url>
  </required_header>
  <id_info>
    <org_study_id>2020P001516</org_study_id>
    <nct_id>NCT04420364</nct_id>
  </id_info>
  <brief_title>Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease</brief_title>
  <official_title>Maintenance Versus Reduction of Immunosuppression for Renal Transplant Patients Hospitalized With COVID-19 Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Brigham and Women's Hospital</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>
      This will be a randomized trial of maintenance versus reduction in immunosuppression in adult&#xD;
      patients (age &gt;18 years old) with functioning renal transplants admitted to hospital with&#xD;
      confirmed COVID-19 disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The optimal management of immunosuppression in renal transplant patients with COVID-19&#xD;
      disease is unclear. On one hand, many centers advocate reduction of immunosuppression in&#xD;
      infected patients, with the rationale that such an approach will unleash the anti-viral&#xD;
      T-cell response. However, on the other hand, some centers advocate there may be rationale to&#xD;
      maintain baseline immunosuppression in order to mitigate against development of an&#xD;
      uncontrolled over-activation of the immune response. The investigators propose to address&#xD;
      this knowledge gap by performing a randomized clinical trial that will test formal&#xD;
      comparisons of maintenance versus reduction in immunosuppression.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Decline in COVID cases&#xD;
  </why_stopped>
  <start_date type="Actual">May 3, 2021</start_date>
  <completion_date type="Actual">May 4, 2021</completion_date>
  <primary_completion_date type="Actual">May 4, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</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-blind, parallel-group, randomized, active-controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>This is a single-blind trial, in that only the assessor will be blinded to the treatment assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in IL-6 concentration from baseline to day 7</measure>
    <time_frame>baseline to day 7</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in IL-6 concentration from baseline to day 28</measure>
    <time_frame>Baseline to day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in T cell response to SARS-CoV-2</measure>
    <time_frame>Baseline to day 7 and day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in titer of serum anti-SARS-CoV-2 antibodies</measure>
    <time_frame>Baseline to day 7 and day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in COVID-19 disease severity score (range 1 to 8; higher worse)</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients needing non-invasive ventilation or intubation</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients developing ANC &lt; 500 cells per microliter</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients developing lymphopenia &lt; 400 cells per microliter</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients developing biopsy-proven acute rejection</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital and 28-day mortality</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse and serious adverse events</measure>
    <time_frame>Through day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID</condition>
  <condition>Kidney Transplant; Complications</condition>
  <condition>Immunosuppression</condition>
  <arm_group>
    <arm_group_label>Maintenance of Immunosuppression</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Maintenance of immunosuppression (defined as no change to pre-admission immunosuppression, or reduction in anti-metabolite by up to 50% (to a minimum of MMF 500 mg per day or azathioprine 50 mg per day)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Reduction of Immunosuppression</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Reduction of immunosuppression (defined as anti-metabolite withdrawal plus reduction of tacrolimus or cyclosporin, to a minimum target trough concentration of 3 ng/mL for tacrolimus and 50 ng/mL for cyclosporin).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Maintenance or reduction of immunosuppression</intervention_name>
    <description>Maintenance versus reduction of immunosuppression</description>
    <arm_group_label>Maintenance of Immunosuppression</arm_group_label>
    <arm_group_label>Reduction of Immunosuppression</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults ≥18 years&#xD;
&#xD;
          -  COVID positive by RT-PCR or serology&#xD;
&#xD;
          -  ≥ 6 months post-transplant&#xD;
&#xD;
          -  use of anti-metabolite (mycophenolate or azathioprine) and calcineurin inhibitor&#xD;
             (cyclosporin or tacrolimus)&#xD;
&#xD;
          -  informed consent; first admission during study period&#xD;
&#xD;
          -  participation within 72 hours of hospitalization&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ICU care or need for invasive ventilation or use of pressors at&#xD;
             screening/randomization&#xD;
&#xD;
          -  COVID-19 disease severity score more than 5 at screening/randomization&#xD;
&#xD;
          -  Known donor specific antibody&#xD;
&#xD;
          -  eGFR &lt;20ml/min/1.73m2&#xD;
&#xD;
          -  hematocrit &lt;24%&#xD;
&#xD;
          -  biopsy proven and treated rejection within last 3 months&#xD;
&#xD;
          -  institutionalized individuals (prisoners)&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  participation in another clinical study with an investigational medicinal product&#xD;
             within 30 days or within 5 half-lives of such, whichever is longer, prior to&#xD;
             randomization and during the study&#xD;
&#xD;
          -  any other conditions, which, in the opinion of the investigator would make the subject&#xD;
             unsuitable.&#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>Jamil Azzi, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Birgham and Women's Hospital</affiliation>
  </overall_official>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>May 3, 2022</last_update_submitted>
  <last_update_submitted_qc>May 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Finnian McCausland</investigator_full_name>
    <investigator_title>Associate Physician</investigator_title>
  </responsible_party>
  <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/NCT04420364
org study id: 2020P001516
nct id: NCT04420364
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This will be a randomized trial of maintenance versus reduction in immunosuppression in adult
      patients (age >18 years old) with functioning renal transplants admitted to hospital with
      confirmed COVID-19 disease.
The optimal management of immunosuppression in renal transplant patients with COVID-19
      disease is unclear. On one hand, many centers advocate reduction of immunosuppression in
      infected patients, with the rationale that such an approach will unleash the anti-viral
      T-cell response. However, on the other hand, some centers advocate there may be rationale to
      maintain baseline immunosuppression in order to mitigate against development of an
      uncontrolled over-activation of the immune response. The investigators propose to address
      this knowledge gap by performing a randomized clinical trial that will test formal
      comparisons of maintenance versus reduction in immunosuppression.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Single-blind, parallel-group, randomized, active-controlled trial
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: This is a single-blind trial, in that only the assessor will be blinded to the treatment assignment.
measure: Change in IL-6 concentration from baseline to day 7
time frame: baseline to day 7
measure: Change in IL-6 concentration from baseline to day 28
time frame: Baseline to day 28
measure: Change in T cell response to SARS-CoV-2
time frame: Baseline to day 7 and day 28
measure: Change in titer of serum anti-SARS-CoV-2 antibodies
time frame: Baseline to day 7 and day 28
measure: Change in COVID-19 disease severity score (range 1 to 8; higher worse)
time frame: Through day 28
measure: Proportion of patients needing non-invasive ventilation or intubation
time frame: Through day 28
measure: Proportion of patients developing ANC < 500 cells per microliter
time frame: Through day 28
measure: Proportion of patients developing lymphopenia < 400 cells per microliter
time frame: Through day 28
measure: Length of hospital stay
time frame: Through day 28
measure: Proportion of patients developing biopsy-proven acute rejection
time frame: Through day 28
measure: In-hospital and 28-day mortality
time frame: Through day 28
measure: Adverse and serious adverse events
time frame: Through day 28
arm group label: Maintenance of Immunosuppression
arm group type: Experimental
description: Maintenance of immunosuppression (defined as no change to pre-admission immunosuppression, or reduction in anti-metabolite by up to 50% (to a minimum of MMF 500 mg per day or azathioprine 50 mg per day)
arm group label: Reduction of Immunosuppression
arm group type: Active Comparator
description: Reduction of immunosuppression (defined as anti-metabolite withdrawal plus reduction of tacrolimus or cyclosporin, to a minimum target trough concentration of 3 ng/mL for tacrolimus and 50 ng/mL for cyclosporin).
intervention type: Other
intervention name: Maintenance or reduction of immunosuppression
description: Maintenance versus reduction of immunosuppression
arm group label: Maintenance of Immunosuppression
arm group label: Reduction of Immunosuppression
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jamil Azzi, MD, PhD
role: Principal Investigator
affiliation: Birgham and Women's Hospital
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Finnian McCausland
investigator title: Associate Physician
sharing ipd: No