<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/NCT04443868</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-IND-02</org_study_id>
    <nct_id>NCT04443868</nct_id>
  </id_info>
  <brief_title>Nitric Oxide Releasing Solution to Treat and Prevent Exacerbation of Mild COVID-19 Infection</brief_title>
  <official_title>Double-Blinded, Placebo-Controlled Parallel, Phase II Clinical Efficacy Study Evaluating NORS To Treat and Prevent the Exacerbation of Infection in Individuals With Documented Mild COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanotize Research and Development corp.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanotize Research and Development corp.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blinded, placebo-controlled parallel, phase II clinical efficacy study&#xD;
      evaluating Nitric Oxide Nasal Irrigation (NONI) for the treatment of COVID-19 in individuals&#xD;
      with mild COVID-19 Infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 50 subjects will be enrolled into one of two cohorts of this study in a ratio of 1:1&#xD;
      (Treatment: Placebo Control). Subjects will be screened and randomized into one of two&#xD;
      parallel cohorts.&#xD;
&#xD;
        -  Treatment (N = up to 25): Subjects will be enrolled and receive daily NONI treatment for&#xD;
           14 days with a follow-up visit on Day 28 post randomization.&#xD;
&#xD;
        -  Placebo (N = up to 25): Subjects will be enrolled and receive a placebo for 14 days with&#xD;
           a follow-up visit on Day 28 post randomization.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No subjects enrolled&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2021</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To Measure the efficacy of NONI compared to saline placebo control to shorten the duration of COVID-19 viral infectivity</measure>
    <time_frame>6 Days</time_frame>
    <description>Measure the SARS-CoV-2 viral load (Cycle threshold) at baseline through Day 6 between NONI and control arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To Measure the virucidal effect of NONI compared to placebo in the nasal cavity in subjects with mild COVID-19 infection</measure>
    <time_frame>2, 4 and 6 days</time_frame>
    <description>Measure the proportion of subjects reaching Ct threshold (ie: unmeasurable viral load) between NONI and control</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To Measure the virucidal effect of NONI compared to placebo in the nasal cavity in subjects with mild COVID-19 infection</measure>
    <time_frame>2, 4 and 6 days</time_frame>
    <description>Measure the difference in time-to Ct threshold (ie: unmeasurable viral load) between NONI and control.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To Measure the efficacy of NONI in prevention of progression of COVID-19</measure>
    <time_frame>28 days</time_frame>
    <description>Measure the proportion of subjects requiring hospitalization or ER/ED visits for COVID-19/flu-like symptoms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life (QoL) in subjects with COVID-19</measure>
    <time_frame>6 days</time_frame>
    <description>Measure the difference in 12-point COVID Symptom PROs score 0-3 (min 0 &amp; max 36) and a QoL score from 0-100 (lower is worse) from baseline between NONI and control arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life in subjects with COVID-19</measure>
    <time_frame>2, 4, 6, 14 and 28 days</time_frame>
    <description>Measure the difference in proportion of subjects experiencing a reduction of ≥ 5 from baseline between NONI and control arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life in subjects with COVID-19</measure>
    <time_frame>2, 4, 6, 14 and 28 days</time_frame>
    <description>Measure the difference in proportion of subjects with reduction to a score of zero from baseline between NONI and control arms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the tolerance of NONI compared to saline placebo in participants with mild COVID-19 infection</measure>
    <time_frame>14 days</time_frame>
    <description>Number of participants lost-to-follow-up,discontinuing study treatment or number of treatments due to intolerance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To measure the tolerance of NONI compared to saline placebo in participants with mild COVID-19 infection</measure>
    <time_frame>14 days</time_frame>
    <description>Severity and frequency of adverse events, pain, discomfort or discontinuations of treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>SARS-CoV Infection</condition>
  <arm_group>
    <arm_group_label>Nitric Oxide Releasing Solution</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Daily nasal irrigation (240mL) 14.4ppm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Isotonic Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Daily nasal irrigation (240mL) 0.9% saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nitric Oxide-Releasing Drug</intervention_name>
    <description>Nasal Spray + Nasal Irrigation</description>
    <arm_group_label>Nitric Oxide Releasing Solution</arm_group_label>
    <arm_group_label>Placebo Isotonic Saline</arm_group_label>
    <other_name>nitric oxide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capable of understanding and providing signed informed consent and ability to adhere&#xD;
             to the requirements and restrictions of this protocol;&#xD;
&#xD;
          -  Men and Women ≥ 18years of age;&#xD;
&#xD;
          -  Internet access and capability and willingness to use to participate in audio or&#xD;
             audio/video engagements with medical professionals, receive texts, emails, and phone&#xD;
             calls from study staff and have a device and reasonable cellular data or other&#xD;
             internet access to submit daily study required information using a smart phone,&#xD;
             tablet, laptop, or desktop computer during the study period;&#xD;
&#xD;
          -  COVID-19 infection confirmed with a laboratory antigen or SARS-CoV-2 RT-PCR nasal&#xD;
             swab;&#xD;
&#xD;
          -  Specimen collected within the past 48 hours;&#xD;
&#xD;
          -  Mild COVID /FLU symptoms which may include no symptoms, fever, cough, sore throat,&#xD;
             malaise, headache, muscle pain, gastrointestinal symptoms, lack of taste or smell&#xD;
             without shortness of breath or dyspnea;&#xD;
&#xD;
          -  Must be willing to use one highly effective birth control method which include:&#xD;
             abstinence, hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal&#xD;
             ring, injectables, and implants); intrauterine device (IUD) or intrauterine system&#xD;
             (IUS); vasectomy and tubal ligation or to use two forms of effective birth control&#xD;
             methods which include: barrier methods of contraception (e.g. male condom, female&#xD;
             condom, cervical cap, diaphragm, contraceptive sponge);&#xD;
&#xD;
               -  Hormonal methods and the IUD must be in use at least 30 days prior to first Study&#xD;
                  drug administration&#xD;
&#xD;
               -  Abstinence and barrier methods must be in use at least 14 days prior to Study&#xD;
                  drug administration&#xD;
&#xD;
               -  Vasectomy must be completed 3 months prior to first Study drug administration; or&#xD;
                  in the alternative that a 0 sperm count will suffice.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Current tracheostomy or laryngectomy;&#xD;
&#xD;
          -  Concomitant respiratory therapy such as oxygen or ventilatory support. Positive airway&#xD;
             pressure for obstructive sleep apnea is permitted if treatment was established with&#xD;
             good compliance at least 3 months before enrolment;&#xD;
&#xD;
          -  Need for hospitalization for any reason;&#xD;
&#xD;
          -  Inability to safely self-administer nasal irrigation&#xD;
&#xD;
          -  Any clinical contraindications, as judged by the Qualified Medical Practitioner;&#xD;
&#xD;
          -  Clinical signs indicative of moderate, severe or critical COVID severity symptoms (as&#xD;
             defined by FDA COVID-19 Guidance Document)&#xD;
&#xD;
          -  Mentally or neurologically disabled patients who are considered not fit to consent to&#xD;
             their participation in the study;&#xD;
&#xD;
          -  Lactating, pregnant or planning to become pregnant during the study period;&#xD;
&#xD;
          -  Diagnosed with prior COVID-19 infection (&gt;48 hours from the time the test is reported&#xD;
             prior to the time of screening).&#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>Mike armstrong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Richmond ENT</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chris Miller, Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>SaNOtize Scientific Advisor</affiliation>
  </overall_official>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>June 20, 2020</study_first_submitted>
  <study_first_submitted_qc>June 20, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>July 12, 2021</last_update_submitted>
  <last_update_submitted_qc>July 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nitric Oxide</mesh_term>
  </intervention_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/NCT04443868
org study id: COVID-IND-02
nct id: NCT04443868
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a double-blinded, placebo-controlled parallel, phase II clinical efficacy study
      evaluating Nitric Oxide Nasal Irrigation (NONI) for the treatment of COVID-19 in individuals
      with mild COVID-19 Infection.
Up to 50 subjects will be enrolled into one of two cohorts of this study in a ratio of 1:1
      (Treatment: Placebo Control). Subjects will be screened and randomized into one of two
      parallel cohorts.

        -  Treatment (N = up to 25): Subjects will be enrolled and receive daily NONI treatment for
           14 days with a follow-up visit on Day 28 post randomization.

        -  Placebo (N = up to 25): Subjects will be enrolled and receive a placebo for 14 days with
           a follow-up visit on Day 28 post randomization.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To Measure the efficacy of NONI compared to saline placebo control to shorten the duration of COVID-19 viral infectivity
time frame: 6 Days
description: Measure the SARS-CoV-2 viral load (Cycle threshold) at baseline through Day 6 between NONI and control arms.
measure: To Measure the virucidal effect of NONI compared to placebo in the nasal cavity in subjects with mild COVID-19 infection
time frame: 2, 4 and 6 days
description: Measure the proportion of subjects reaching Ct threshold (ie: unmeasurable viral load) between NONI and control
measure: To Measure the virucidal effect of NONI compared to placebo in the nasal cavity in subjects with mild COVID-19 infection
time frame: 2, 4 and 6 days
description: Measure the difference in time-to Ct threshold (ie: unmeasurable viral load) between NONI and control.
measure: To Measure the efficacy of NONI in prevention of progression of COVID-19
time frame: 28 days
description: Measure the proportion of subjects requiring hospitalization or ER/ED visits for COVID-19/flu-like symptoms
measure: To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life (QoL) in subjects with COVID-19
time frame: 6 days
description: Measure the difference in 12-point COVID Symptom PROs score 0-3 (min 0 & max 36) and a QoL score from 0-100 (lower is worse) from baseline between NONI and control arms.
measure: To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life in subjects with COVID-19
time frame: 2, 4, 6, 14 and 28 days
description: Measure the difference in proportion of subjects experiencing a reduction of ≥ 5 from baseline between NONI and control arms.
measure: To measure reduction of patient reported outcome (PRO) of clinical cold score symptoms and quality of life in subjects with COVID-19
time frame: 2, 4, 6, 14 and 28 days
description: Measure the difference in proportion of subjects with reduction to a score of zero from baseline between NONI and control arms.
measure: To measure the tolerance of NONI compared to saline placebo in participants with mild COVID-19 infection
time frame: 14 days
description: Number of participants lost-to-follow-up,discontinuing study treatment or number of treatments due to intolerance
measure: To measure the tolerance of NONI compared to saline placebo in participants with mild COVID-19 infection
time frame: 14 days
description: Severity and frequency of adverse events, pain, discomfort or discontinuations of treatment.
arm group label: Nitric Oxide Releasing Solution
arm group type: Experimental
description: Daily nasal irrigation (240mL) 14.4ppm
arm group label: Placebo Isotonic Saline
arm group type: Placebo Comparator
description: Daily nasal irrigation (240mL) 0.9% saline
intervention type: Drug
intervention name: Nitric Oxide-Releasing Drug
description: Nasal Spray + Nasal Irrigation
arm group label: Nitric Oxide Releasing Solution
arm group label: Placebo Isotonic Saline
other name: nitric oxide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mike armstrong, MD
role: Principal Investigator
affiliation: Richmond ENT
last name: Chris Miller, Ph.D
role: Study Director
affiliation: SaNOtize Scientific Advisor
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Severe Acute Respiratory Syndrome
mesh term: Nitric Oxide
sharing ipd: No