<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/NCT04468646</url>
  </required_header>
  <id_info>
    <org_study_id>UniversityHSL-NK1R</org_study_id>
    <nct_id>NCT04468646</nct_id>
  </id_info>
  <brief_title>To Determine the Efficacy of Neurokinin 1 Receptor Antagonist as a Therapeutic Tool Against Cytokine Storm and Respiratory Failure in Covid-19 Patients</brief_title>
  <official_title>To Determine the Efficacy of Neurokinin 1 Receptor Antagonist as a Therapeutic Tool Against Cytokine Storm and Respiratory Failure in Covid-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prof. Dr. Fridoon Jawad Ahmad</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Lahore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bahria International Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Health Sciences Lahore</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 is a randomized, randomized controlled trial to investigate the efficacy and safety of&#xD;
      Neurokinin-1 Receptor (NK-1R) 80 mg orally given daily to treat cytokine storm causing&#xD;
      inflammatory lung injury and respiratory failure associated with severe or critical COVID-19&#xD;
      infection. NK-1R is the receptor of Substance P (SP) and responsible for its functionality.&#xD;
      Here, we propose that SP via its tachykinin receptor, NK-1R may cause inflammation in&#xD;
      Covid-19 infection. It may initiate the cytokine storming via binding to its receptor NK-1&#xD;
      and many inflammatory mediators are released. If SP release is reduced by NK-1R antagonist,&#xD;
      it may control the cytokine storming and hence the hyper-responsiveness of the respiratory&#xD;
      tract through reduction in cytokine storming It may serve as the treatment strategy for&#xD;
      Covid-19 infected patients.&#xD;
&#xD;
      Patients fulfilling the inclusion criteria will be enrolled after giving consent. They wll be&#xD;
      randomized to treatment with either NK-1R antagonist or placebo in addition to Dexamethasone&#xD;
      as a standard treatment given to both groups for Covid-19 infection as per the protocol at&#xD;
      the treating hospital. Inflammatory lab markers as detailed should be collected once per day&#xD;
      in the morning, preferably at the same time every morning. All enrolled participants will&#xD;
      have whole blood collected for whole genome sequencing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
      To evaluate the clinical outcomes of Neurokinin 1 Receptor antagonist in Covid-19 patients&#xD;
      against the usual treatments as controls&#xD;
&#xD;
      Dosage Aprepitant capsules may be given to patients from 3-5 days fosaprepitant dimeglumine&#xD;
      (Injection 115mg, prodrug form of aprepitant) may be substituted for oral drug in case of&#xD;
      critical patients May be taken with or without food&#xD;
&#xD;
      Administration One capsule of Aprepitant once a day for 3-5 days&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">August 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 15, 2020</primary_completion_date>
  <phase>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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to improvement on a 7-point ordinal scale as compared to baseline</measure>
    <time_frame>14 days or discharge</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>total in-hospital days and the total duration</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction from baseline of NRS for cough</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction from baseline of NRS for nausea</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to normalization of fever for at least 48 hours</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to improvement in oxygenation for at least 48 hours</measure>
    <time_frame>14 days or discharge</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Neurokinin 1 Receptor, Substance P, Respiratory Illness, Inflammation, Covid-19, Coronavirus</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>matching placebo drug</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NK-1R antagonist group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>80 mg daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NK-1R antagonist</intervention_name>
    <description>NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days</description>
    <arm_group_label>NK-1R antagonist group</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; 18 yrs&#xD;
&#xD;
          -  Both genders&#xD;
&#xD;
          -  Lab Confirmed COVID-19 infection by PCR or plasma positive of specific antibody&#xD;
             against COVID-19&#xD;
&#xD;
          -  In hospital treatment ≥ 72 hours&#xD;
&#xD;
          -  Admitted patients&#xD;
&#xD;
          -  Severe Disease (Respiratory rate &gt;=30/min; or (b) Rest SPO2&lt;=90%; or (c)&#xD;
             PaO2/FiO2&lt;=300 mmHg) or&#xD;
&#xD;
          -  Critical Phase (Respiratory failure and needs mechanical ventilation; or Shock occurs;&#xD;
             or Multiple organ failure and needs ICU monitoring)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are not willing to give consent&#xD;
&#xD;
          -  known HIV,HBV, HCV infection&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Bahria International Hospital</name>
      <address>
        <city>Lahore</city>
        <state>Punjab</state>
        <zip>53720</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ahad Qayyum, MBBS,MRCP</last_name>
      <phone>00924235340135</phone>
      <phone_ext>7</phone_ext>
      <email>lhrhospital@bahriatown.com.pk</email>
    </contact>
    <contact_backup>
      <last_name>Muhammad Asim o Rana, MBBS</last_name>
      <phone>00923435807006</phone>
      <email>lhrhospital@bahriatown.com.pk</email>
    </contact_backup>
    <investigator>
      <last_name>Riffat Mehboob, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Fridoon Jawad Ahmad, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Ahad Qayyum, MBBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Muhammad Asim Rana, MBBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Javed Akram, MBBS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>July 10, 2020</last_update_submitted>
  <last_update_submitted_qc>July 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Health Sciences Lahore</investigator_affiliation>
    <investigator_full_name>Prof. Dr. Fridoon Jawad Ahmad</investigator_full_name>
    <investigator_title>Professor, head of Physiology department</investigator_title>
  </responsible_party>
  <keyword>neurokinin 1 receptor</keyword>
  <keyword>Substance P</keyword>
  <keyword>Respiratory illness</keyword>
  <keyword>inflammation</keyword>
  <keyword>Covid-19</keyword>
  <keyword>Coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Cytokine Release Syndrome</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/NCT04468646
org study id: UniversityHSL-NK1R
nct id: NCT04468646
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a randomized, randomized controlled trial to investigate the efficacy and safety of
      Neurokinin-1 Receptor (NK-1R) 80 mg orally given daily to treat cytokine storm causing
      inflammatory lung injury and respiratory failure associated with severe or critical COVID-19
      infection. NK-1R is the receptor of Substance P (SP) and responsible for its functionality.
      Here, we propose that SP via its tachykinin receptor, NK-1R may cause inflammation in
      Covid-19 infection. It may initiate the cytokine storming via binding to its receptor NK-1
      and many inflammatory mediators are released. If SP release is reduced by NK-1R antagonist,
      it may control the cytokine storming and hence the hyper-responsiveness of the respiratory
      tract through reduction in cytokine storming It may serve as the treatment strategy for
      Covid-19 infected patients.

      Patients fulfilling the inclusion criteria will be enrolled after giving consent. They wll be
      randomized to treatment with either NK-1R antagonist or placebo in addition to Dexamethasone
      as a standard treatment given to both groups for Covid-19 infection as per the protocol at
      the treating hospital. Inflammatory lab markers as detailed should be collected once per day
      in the morning, preferably at the same time every morning. All enrolled participants will
      have whole blood collected for whole genome sequencing.
Objective:

      To evaluate the clinical outcomes of Neurokinin 1 Receptor antagonist in Covid-19 patients
      against the usual treatments as controls

      Dosage Aprepitant capsules may be given to patients from 3-5 days fosaprepitant dimeglumine
      (Injection 115mg, prodrug form of aprepitant) may be substituted for oral drug in case of
      critical patients May be taken with or without food

      Administration One capsule of Aprepitant once a day for 3-5 days
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Time to improvement on a 7-point ordinal scale as compared to baseline
time frame: 14 days or discharge
measure: total in-hospital days and the total duration
time frame: 14 days or discharge
measure: Treatment and prevention of inflammatory lung injury as measured by change in baseline of interleukin-6 (IL-6)
time frame: 14 days or discharge
measure: Rate of Decline of COVID-19 viral load assessed by RT-PCR from nasopharyngeal samples
time frame: 14 days or discharge
measure: Reduction from baseline of NRS for cough
time frame: 14 days or discharge
measure: Reduction from baseline of NRS for nausea
time frame: 14 days or discharge
measure: Time to normalization of fever for at least 48 hours
time frame: 14 days or discharge
measure: Time to improvement in oxygenation for at least 48 hours
time frame: 14 days or discharge
arm group label: Placebo
arm group type: Placebo Comparator
description: matching placebo drug
arm group label: NK-1R antagonist group
arm group type: Experimental
description: 80 mg daily
intervention type: Drug
intervention name: NK-1R antagonist
description: NK-1R antagonist, 80 mg daily once for 3-5 days along with dexamethasone 6 mg daily for 5 days
arm group label: NK-1R antagonist group
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Pakistan
responsible party type: Sponsor-Investigator
investigator affiliation: University of Health Sciences Lahore
investigator full name: Prof. Dr. Fridoon Jawad Ahmad
investigator title: Professor, head of Physiology department
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Respiratory Insufficiency
mesh term: Inflammation
mesh term: Cytokine Release Syndrome
sharing ipd: No