<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/NCT04465604</url>
  </required_header>
  <id_info>
    <org_study_id>RAC # 2201072</org_study_id>
    <secondary_id>H-01-R-007</secondary_id>
    <nct_id>NCT04465604</nct_id>
  </id_info>
  <brief_title>Hypertonic Saline for COVID-19 Symptoms</brief_title>
  <official_title>HYPERTONIC SALINE COATED FACE MASK FOR REDUCING RESPIRATORY SYMPTOM SEVERITY IN PATIENTS WITH COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King Faisal Specialist Hospital &amp; Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>King Faisal Specialist Hospital &amp; Research Center</source>
  <oversight_info>
    <has_dmc>No</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>
      Rationale:&#xD;
&#xD;
      Coronavirus disease 2019 (COVID-19) is spreading rapidly in the world with no proven&#xD;
      effective therapy to date. Some patients with COVID-19 develop sever respiratory disease&#xD;
      requiring ICU care. There is in vitro evidence that hypertonic saline (HTS) may be beneficial&#xD;
      in reducing the inflammatory component in similar viral illnesses.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To assess whether wearing a face mask sprayed with HTS (in addition to other COVID-19&#xD;
      treatments) leads to decreasing the severity of the respiratory symptoms resulting from&#xD;
      COVID-19.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      Multi-centre trial&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      Any patient older than 18 years of age with confirmed COVID-19 diagnosis who has any of the&#xD;
      following respiratory symptoms or signs:&#xD;
&#xD;
        -  cough,&#xD;
&#xD;
        -  shortness of breath,&#xD;
&#xD;
        -  tachypnea (respiratory rate of 20 breaths / minute or more),&#xD;
&#xD;
        -  hypoxemia (O2 saturation 90% or less on room air)&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      Participants will be asked to wear a face mask for 20-30 minutes every 6 hours for the&#xD;
      duration of their respiratory symptoms and/or signs. This inside surface of the face mask&#xD;
      will be sprayed with 10-15 ml of HTS and allowed to air dry before the participant is&#xD;
      permitted to wear it. A new face mask will be given to the patient every 24 hours. All&#xD;
      participants will continue to receive their other COVID-19 treatments as per local hospital&#xD;
      guidelines.&#xD;
&#xD;
      Main study parameter:&#xD;
&#xD;
      Improvement of the respiratory symptoms and signs on repeated measurement.&#xD;
&#xD;
      Nature and extent of the burden and risks associated with participation, benefit:&#xD;
&#xD;
      The burden of COVID-19 is very severe world wide. The trial duration is 3 months, with&#xD;
      potential extension if deemed needed by interim analysis at the end of 3 months. There are no&#xD;
      additional risks for participation in this study as only face masks will be used with no&#xD;
      additional medications being given to the participants. In the future, the results of this&#xD;
      study could lead to improved care for COVID-19 patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Since its emergence as severe outbreak in China in December 2019, coronavirus disease 2019&#xD;
      (COVID-19) has spread so rapidly in the world that more than 780,000 cases have so far been&#xD;
      reported worldwide and since then the WHO has declared it as a pandemic. The rapid spread of&#xD;
      the disease is imposing major threats on healthcare systems in many countries in the world&#xD;
      The major threat to these healthcare systems so far has been the large number of patients who&#xD;
      will need respiratory support (ventilators) because of the severe lung injury associated with&#xD;
      COVID-19.This disease shares similar pathogenetic, epidemiological and clinical features to&#xD;
      the two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS]&#xD;
      and Middle East respiratory syndrome [MERS]) to COVID-19. However little is currently known&#xD;
      about SARS-CoV-2 with no established therapy or vaccine.&#xD;
&#xD;
      Lai et al in their 2005 publication showed that &quot;Even with a relatively high virus load&#xD;
      (SARS-CoV) in the droplet, rapid loss of infectivity was observed for paper and cotton&#xD;
      material&quot; and that &quot;all disinfectants (used in the study) reduced the virus load (SARS-CoV)&#xD;
      by 13 log within 5 min after incubation&quot;. In addition, it has been shown that viruses&#xD;
      (including corona family of viruses) can be de-activated when they come in contact with&#xD;
      surfaces covered with sodium chloride (table salt). This can be explained by &quot;physical&#xD;
      destruction of virus during recrystallization of coated salts. When the salt-coated fiber is&#xD;
      exposed to virus aerosols, salt crystals below the aerosol droplet dissolve to increase&#xD;
      osmotic pressure to virus. Due to evaporation, the salt concentration of the droplet&#xD;
      significantly increases and reaches the solubility limit, leading to recrystallization of&#xD;
      salt. As a consequence, virus particles are exposed to increasing osmotic pressure during the&#xD;
      drying process and are physically damaged by crystallization.&quot; In 1961, Spier et al showed&#xD;
      that viral replication is inhibited by the presence of chloride / halide salts. In addition,&#xD;
      a recent report showed that non-myeloid cells (e.g. epithelial, fibroblast and hepatic cells)&#xD;
      have an innate immune mechanism, which is augmented in the presence of salt (NaCl). The same&#xD;
      report also showed that, in cell culture models, DNA, RNA, enveloped and non-enveloped&#xD;
      viruses are all inhibited in the presence of NaCl. The antiviral effect was dependent on the&#xD;
      availability of chloride ions (and not sodium ions). In the presence viral infection and the&#xD;
      availability of NaCl, cells utilize the chloride ions to produce hypochlorous acid (HOCl).&#xD;
      Since HOCl is the active ingredient in bleach, which is known to have an antiviral effect,&#xD;
      the mechanism could be augmented by supplying chloride ions through NaCl to treat viral&#xD;
      infections. The Edinburgh and Lothians Viral Intervention Study (ELVIS), a pilot RCT of&#xD;
      hypertonic saline nasal irrigation and gargling (HSNIG) versus standard care in adults with&#xD;
      URTI showed a reduction in the duration of illness by 1.9 days (p = 0.01), less&#xD;
      over-the-counter medications use by 36% (p = 0.004), less disease transmission within&#xD;
      household contacts by 35% (p = 0.006) and less viral shedding by ≥0.5 log10/day (p = 0.04).&#xD;
&#xD;
      Hypertonic saline (HTS) has also been shown to have anti-inflammatory effects on lung&#xD;
      epithelium. In addition, inhaled HTS has been shown to have beneficial effects when used for&#xD;
      patients with lung diseases (e.g. cystic fibrosis).&#xD;
&#xD;
      Therefore, the combination of the antiviral properties on surfaces and the anti-inflammatory&#xD;
      effects of HTS renders such widely available, affordable and cheap therapy amenable for&#xD;
      exploring as potentially beneficial in reducing the severity of lung injury in patients with&#xD;
      symptomatic COVID-19 with very minimal risk to the patients.&#xD;
&#xD;
      This proposal aims at testing the effect of spraying the routinely used face masks (or for&#xD;
      that matter any material to cover nose and mouth) with HTS on the severity of respiratory&#xD;
      symptoms and signs of patients with confirmed COVID-19. In addition, the rate for ICU&#xD;
      utilization will be monitored.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2021</start_date>
  <completion_date type="Anticipated">May 2022</completion_date>
  <primary_completion_date type="Anticipated">November 1, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>The sample size was based on the following assumptions: Poor response rate to HTS is set at 10% or less; Good response to HTS is set at 30% or more ;One-sided Alph error probability is set to &lt; 0.05 (i.e. p &lt; 0.05) and Power to detect rate difference between good response and poor response to HTS is at least 80%. Using the Fleming single-arm group-sequential design (Fleming 1982) Based on these assumptions; a sample size of N=25 patients is expected to achieve a power of 84% of detecting enough activity by HTS (p&lt;0.05 one-sided) of improving respiratory parameters of COVID19 patients. This will be achieved if the true remission rate difference between a poor and good HTS is 20%. Considering the dropout rate of 25%, a minimum of 50 patients will be enrolled. This will ensure more than 90% power to detect at least 20% positive effect of HTS</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Improvement of respiratory symptoms</measure>
    <time_frame>Throughout hospital stay on average 21 days</time_frame>
    <description>Cough and / or shortness of breath</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Improvement of respiratory signs</measure>
    <time_frame>Throughout hospital stay on average 21 days</time_frame>
    <description>Respiratory rate and / or need for supplemental oxygen</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ICU admission</measure>
    <time_frame>Throughout hospital stay on average 21 days</time_frame>
    <description>Rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical ventilation</measure>
    <time_frame>Throughout hospital stay on average 21 days</time_frame>
    <description>Rate</description>
  </secondary_outcome>
  <enrollment type="Anticipated">50</enrollment>
  <condition>COVID-19</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Wearing surgical face mask sprayed with hypertonic saline</intervention_name>
    <description>The inner surface of a standard surgical face mask will sprayed by 10 to 15 ml of HTS (6% w/v Saline solution prepared by adding 6 gram NaCl to 100 ml of water if not commercially available) and allowed to air dry. The participant will wear the face mask for 20-30 minutes every 6 hours until discharge, intubation for mechanical ventilation or death. A new HTS sprayed mask will be worn by the participant every 24 hours. The data items will be collected on daily basis</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 years and older&#xD;
&#xD;
          -  confirmed diagnosis of COVID-19 by PCR and&#xD;
&#xD;
          -  Any of the following&#xD;
&#xD;
               -  cough&#xD;
&#xD;
               -  shortness of breath&#xD;
&#xD;
               -  Respiratory rate more than 20 per minute or&#xD;
&#xD;
               -  oxygen saturation 90% or less on room air&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age younger than 18 years&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Participation in other COVID-19 intervention trial&#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>Ali Alshanqeeti, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>King Faisal Specialsit Hospital and Research Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ali Alshanqeeti, MD</last_name>
    <phone>+966114427094</phone>
    <email>ashanqeeti@kfshrc.edu.sa</email>
  </overall_contact>
  <location>
    <facility>
      <name>King Faisal Specialist Hospital and Research Center</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ali Alshanqeeti, MD</last_name>
      <phone>+966114427094</phone>
      <email>ashanqeeti@kfshrc.edu.sa</email>
    </contact>
  </location>
  <location_countries>
    <country>Saudi Arabia</country>
  </location_countries>
  <reference>
    <citation>Lai MY, Cheng PK, Lim WW. Survival of severe acute respiratory syndrome coronavirus. Clin Infect Dis. 2005 Oct 1;41(7):e67-71. doi: 10.1086/433186. Epub 2005 Aug 22.</citation>
    <PMID>16142653</PMID>
  </reference>
  <reference>
    <citation>Quan FS, Rubino I, Lee SH, Koch B, Choi HJ. Universal and reusable virus deactivation system for respiratory protection. Sci Rep. 2017 Jan 4;7:39956. doi: 10.1038/srep39956.</citation>
    <PMID>28051158</PMID>
  </reference>
  <reference>
    <citation>Speir, R. W. (1961). Effect of Several Inorganic Salts on Infectivity of Mengo Virus. Proceedings of the Society for Experimental Biology and Medicine, 106(2), 402-404. https://doi.org/10.3181/00379727-106-26352</citation>
  </reference>
  <reference>
    <citation>Ramalingam S, Cai B, Wong J, Twomey M, Chen R, Fu RM, Boote T, McCaughan H, Griffiths SJ, Haas JG. Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Sci Rep. 2018 Sep 11;8(1):13630. doi: 10.1038/s41598-018-31936-y.</citation>
    <PMID>30206371</PMID>
  </reference>
  <reference>
    <citation>Ramalingam S, Graham C, Dove J, Morrice L, Sheikh A. A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Sci Rep. 2019 Jan 31;9(1):1015. doi: 10.1038/s41598-018-37703-3.</citation>
    <PMID>30705369</PMID>
  </reference>
  <reference>
    <citation>Wright FL, Gamboni F, Moore EE, Nydam TL, Mitra S, Silliman CC, Banerjee A. Hyperosmolarity invokes distinct anti-inflammatory mechanisms in pulmonary epithelial cells: evidence from signaling and transcription layers. PLoS One. 2014 Dec 5;9(12):e114129. doi: 10.1371/journal.pone.0114129. eCollection 2014.</citation>
    <PMID>25479425</PMID>
  </reference>
  <reference>
    <citation>Nydam TL, Moore EE, McIntyre RC Jr, Wright FL, Gamboni-Robertson F, Eckels PC, Banerjee A. Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells. Shock. 2009 May;31(5):466-72. doi: 10.1097/SHK.0b013e31818ec47d.</citation>
    <PMID>18948845</PMID>
  </reference>
  <reference>
    <citation>Gamboni F, Anderson C, Mitra S, Reisz JA, Nemkov T, Dzieciatkowska M, Jones KL, Hansen KC, D'Alessandro A, Banerjee A. Hypertonic Saline Primes Activation of the p53-p21 Signaling Axis in Human Small Airway Epithelial Cells That Prevents Inflammation Induced by Pro-inflammatory Cytokines. J Proteome Res. 2016 Oct 7;15(10):3813-3826. doi: 10.1021/acs.jproteome.6b00602. Epub 2016 Aug 29.</citation>
    <PMID>27529569</PMID>
  </reference>
  <reference>
    <citation>Mitra S, Schiller D, Anderson C, Gamboni F, D'Alessandro A, Kelher M, Silliman CC, Banerjee A, Jones KL. Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. PLoS One. 2017 Dec 18;12(12):e0189536. doi: 10.1371/journal.pone.0189536. eCollection 2017.</citation>
    <PMID>29253007</PMID>
  </reference>
  <reference>
    <citation>Deree J, Martins JO, Leedom A, Lamon B, Putnam J, de Campos T, Hoyt DB, Wolf P, Coimbra R. Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation-induced pulmonary inflammation through attenuation of neutrophil degranulation and proinflammatory mediator synthesis. J Trauma. 2007 Jan;62(1):104-11. doi: 10.1097/TA.0b013e31802d96cb.</citation>
    <PMID>17215740</PMID>
  </reference>
  <reference>
    <citation>Pimentel RN, Petroni RC, Barbeiro HV, Barbeiro DF, Andrade MM, Ariga SK, Soriano FG. Hypertonic solution-induced preconditioning reduces inflammation and mortality rate. J Inflamm (Lond). 2019 Jul 3;16:16. doi: 10.1186/s12950-019-0220-4. eCollection 2019.</citation>
    <PMID>31312113</PMID>
  </reference>
  <reference>
    <citation>Reeves EP, Molloy K, Pohl K, McElvaney NG. Hypertonic saline in treatment of pulmonary disease in cystic fibrosis. ScientificWorldJournal. 2012;2012:465230. doi: 10.1100/2012/465230. Epub 2012 May 3.</citation>
    <PMID>22645424</PMID>
  </reference>
  <reference>
    <citation>Reeves EP, McCarthy C, McElvaney OJ, Vijayan MS, White MM, Dunlea DM, Pohl K, Lacey N, McElvaney NG. Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function. World J Crit Care Med. 2015 Aug 4;4(3):179-91. doi: 10.5492/wjccm.v4.i3.179. eCollection 2015 Aug 4.</citation>
    <PMID>26261770</PMID>
  </reference>
  <reference>
    <citation>Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, Azar A, Baroody FM, Bachert C, Canonica GW, Chacko T, Cingi C, Ciprandi G, Corey J, Cox LS, Creticos PS, Custovic A, Damask C, DeConde A, DelGaudio JM, Ebert CS, Eloy JA, Flanagan CE, Fokkens WJ, Franzese C, Gosepath J, Halderman A, Hamilton RG, Hoffman HJ, Hohlfeld JM, Houser SM, Hwang PH, Incorvaia C, Jarvis D, Khalid AN, Kilpelainen M, Kingdom TT, Krouse H, Larenas-Linnemann D, Laury AM, Lee SE, Levy JM, Luong AU, Marple BF, McCoul ED, McMains KC, Melen E, Mims JW, Moscato G, Mullol J, Nelson HS, Patadia M, Pawankar R, Pfaar O, Platt MP, Reisacher W, Rondon C, Rudmik L, Ryan M, Sastre J, Schlosser RJ, Settipane RA, Sharma HP, Sheikh A, Smith TL, Tantilipikorn P, Tversky JR, Veling MC, Wang Y, Westman M, Wickman M, Zacharek M. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352. doi: 10.1002/alr.22073.</citation>
    <PMID>29438602</PMID>
  </reference>
  <reference>
    <citation>Tarrant BJ, Le Maitre C, Romero L, Steward R, Button BM, Thompson BR, Holland AE. Mucoactive agents for chronic, non-cystic fibrosis lung disease: A systematic review and meta-analysis. Respirology. 2017 Aug;22(6):1084-1092. doi: 10.1111/resp.13047. Epub 2017 Apr 11.</citation>
    <PMID>28397992</PMID>
  </reference>
  <reference>
    <citation>Lin L, Chen Z, Cao Y, Sun G. Normal saline solution nasal-pharyngeal irrigation improves chronic cough associated with allergic rhinitis. Am J Rhinol Allergy. 2017 Mar 1;31(2):96-104. doi: 10.2500/ajra.2017.31.4418.</citation>
    <PMID>28452705</PMID>
  </reference>
  <reference>
    <citation>Liedtke CM. Understanding the cellular mechanism for inhaled hyperosmotic saline therapy for patients with cystic fibrosis. Focus on &quot;Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors&quot;. Am J Physiol Cell Physiol. 2013 Dec 1;305(11):C1096-7. doi: 10.1152/ajpcell.00250.2013. Epub 2013 Aug 28. No abstract available.</citation>
    <PMID>23986195</PMID>
  </reference>
  <reference>
    <citation>Huiberts A, Zweijpfenning SMH, Pennings LJ, Boeree MJ, van Ingen J, Magis-Escurra C, Hoefsloot W. Outcomes of hypertonic saline inhalation as a treatment modality in nontuberculous mycobacterial pulmonary disease. Eur Respir J. 2019 Jul 11;54(1):1802143. doi: 10.1183/13993003.02143-2018. Print 2019 Jul. No abstract available.</citation>
    <PMID>31000680</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>March 4, 2021</last_update_submitted>
  <last_update_submitted_qc>March 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 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>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/NCT04465604
org study id: RAC # 2201072
secondary id: H-01-R-007
nct id: NCT04465604
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Rationale:

      Coronavirus disease 2019 (COVID-19) is spreading rapidly in the world with no proven
      effective therapy to date. Some patients with COVID-19 develop sever respiratory disease
      requiring ICU care. There is in vitro evidence that hypertonic saline (HTS) may be beneficial
      in reducing the inflammatory component in similar viral illnesses.

      Objective:

      To assess whether wearing a face mask sprayed with HTS (in addition to other COVID-19
      treatments) leads to decreasing the severity of the respiratory symptoms resulting from
      COVID-19.

      Study design:

      Multi-centre trial

      Study population:

      Any patient older than 18 years of age with confirmed COVID-19 diagnosis who has any of the
      following respiratory symptoms or signs:

        -  cough,

        -  shortness of breath,

        -  tachypnea (respiratory rate of 20 breaths / minute or more),

        -  hypoxemia (O2 saturation 90% or less on room air)

      Intervention:

      Participants will be asked to wear a face mask for 20-30 minutes every 6 hours for the
      duration of their respiratory symptoms and/or signs. This inside surface of the face mask
      will be sprayed with 10-15 ml of HTS and allowed to air dry before the participant is
      permitted to wear it. A new face mask will be given to the patient every 24 hours. All
      participants will continue to receive their other COVID-19 treatments as per local hospital
      guidelines.

      Main study parameter:

      Improvement of the respiratory symptoms and signs on repeated measurement.

      Nature and extent of the burden and risks associated with participation, benefit:

      The burden of COVID-19 is very severe world wide. The trial duration is 3 months, with
      potential extension if deemed needed by interim analysis at the end of 3 months. There are no
      additional risks for participation in this study as only face masks will be used with no
      additional medications being given to the participants. In the future, the results of this
      study could lead to improved care for COVID-19 patients.
Since its emergence as severe outbreak in China in December 2019, coronavirus disease 2019
      (COVID-19) has spread so rapidly in the world that more than 780,000 cases have so far been
      reported worldwide and since then the WHO has declared it as a pandemic. The rapid spread of
      the disease is imposing major threats on healthcare systems in many countries in the world
      The major threat to these healthcare systems so far has been the large number of patients who
      will need respiratory support (ventilators) because of the severe lung injury associated with
      COVID-19.This disease shares similar pathogenetic, epidemiological and clinical features to
      the two previously reported coronavirus epidemics (severe acute respiratory syndrome [SARS]
      and Middle East respiratory syndrome [MERS]) to COVID-19. However little is currently known
      about SARS-CoV-2 with no established therapy or vaccine.

      Lai et al in their 2005 publication showed that "Even with a relatively high virus load
      (SARS-CoV) in the droplet, rapid loss of infectivity was observed for paper and cotton
      material" and that "all disinfectants (used in the study) reduced the virus load (SARS-CoV)
      by 13 log within 5 min after incubation". In addition, it has been shown that viruses
      (including corona family of viruses) can be de-activated when they come in contact with
      surfaces covered with sodium chloride (table salt). This can be explained by "physical
      destruction of virus during recrystallization of coated salts. When the salt-coated fiber is
      exposed to virus aerosols, salt crystals below the aerosol droplet dissolve to increase
      osmotic pressure to virus. Due to evaporation, the salt concentration of the droplet
      significantly increases and reaches the solubility limit, leading to recrystallization of
      salt. As a consequence, virus particles are exposed to increasing osmotic pressure during the
      drying process and are physically damaged by crystallization." In 1961, Spier et al showed
      that viral replication is inhibited by the presence of chloride / halide salts. In addition,
      a recent report showed that non-myeloid cells (e.g. epithelial, fibroblast and hepatic cells)
      have an innate immune mechanism, which is augmented in the presence of salt (NaCl). The same
      report also showed that, in cell culture models, DNA, RNA, enveloped and non-enveloped
      viruses are all inhibited in the presence of NaCl. The antiviral effect was dependent on the
      availability of chloride ions (and not sodium ions). In the presence viral infection and the
      availability of NaCl, cells utilize the chloride ions to produce hypochlorous acid (HOCl).
      Since HOCl is the active ingredient in bleach, which is known to have an antiviral effect,
      the mechanism could be augmented by supplying chloride ions through NaCl to treat viral
      infections. The Edinburgh and Lothians Viral Intervention Study (ELVIS), a pilot RCT of
      hypertonic saline nasal irrigation and gargling (HSNIG) versus standard care in adults with
      URTI showed a reduction in the duration of illness by 1.9 days (p = 0.01), less
      over-the-counter medications use by 36% (p = 0.004), less disease transmission within
      household contacts by 35% (p = 0.006) and less viral shedding by ≥0.5 log10/day (p = 0.04).

      Hypertonic saline (HTS) has also been shown to have anti-inflammatory effects on lung
      epithelium. In addition, inhaled HTS has been shown to have beneficial effects when used for
      patients with lung diseases (e.g. cystic fibrosis).

      Therefore, the combination of the antiviral properties on surfaces and the anti-inflammatory
      effects of HTS renders such widely available, affordable and cheap therapy amenable for
      exploring as potentially beneficial in reducing the severity of lung injury in patients with
      symptomatic COVID-19 with very minimal risk to the patients.

      This proposal aims at testing the effect of spraying the routinely used face masks (or for
      that matter any material to cover nose and mouth) with HTS on the severity of respiratory
      symptoms and signs of patients with confirmed COVID-19. In addition, the rate for ICU
      utilization will be monitored.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The sample size was based on the following assumptions: Poor response rate to HTS is set at 10% or less; Good response to HTS is set at 30% or more ;One-sided Alph error probability is set to < 0.05 (i.e. p < 0.05) and Power to detect rate difference between good response and poor response to HTS is at least 80%. Using the Fleming single-arm group-sequential design (Fleming 1982) Based on these assumptions; a sample size of N=25 patients is expected to achieve a power of 84% of detecting enough activity by HTS (p<0.05 one-sided) of improving respiratory parameters of COVID19 patients. This will be achieved if the true remission rate difference between a poor and good HTS is 20%. Considering the dropout rate of 25%, a minimum of 50 patients will be enrolled. This will ensure more than 90% power to detect at least 20% positive effect of HTS
primary purpose: Treatment
masking: None (Open Label)
measure: Improvement of respiratory symptoms
time frame: Throughout hospital stay on average 21 days
description: Cough and / or shortness of breath
measure: Improvement of respiratory signs
time frame: Throughout hospital stay on average 21 days
description: Respiratory rate and / or need for supplemental oxygen
measure: ICU admission
time frame: Throughout hospital stay on average 21 days
description: Rate
measure: Mechanical ventilation
time frame: Throughout hospital stay on average 21 days
description: Rate
intervention type: Other
intervention name: Wearing surgical face mask sprayed with hypertonic saline
description: The inner surface of a standard surgical face mask will sprayed by 10 to 15 ml of HTS (6% w/v Saline solution prepared by adding 6 gram NaCl to 100 ml of water if not commercially available) and allowed to air dry. The participant will wear the face mask for 20-30 minutes every 6 hours until discharge, intubation for mechanical ventilation or death. A new HTS sprayed mask will be worn by the participant every 24 hours. The data items will be collected on daily basis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ali Alshanqeeti, MD
role: Principal Investigator
affiliation: King Faisal Specialsit Hospital and Research Center
last name: Ali Alshanqeeti, MD
phone: +966114427094
email: ashanqeeti@kfshrc.edu.sa
facility: 
status: Recruiting
contact: 
country: Saudi Arabia
citation: Lai MY, Cheng PK, Lim WW. Survival of severe acute respiratory syndrome coronavirus. Clin Infect Dis. 2005 Oct 1;41(7):e67-71. doi: 10.1086/433186. Epub 2005 Aug 22.
PMID: 16142653
citation: Quan FS, Rubino I, Lee SH, Koch B, Choi HJ. Universal and reusable virus deactivation system for respiratory protection. Sci Rep. 2017 Jan 4;7:39956. doi: 10.1038/srep39956.
PMID: 28051158
citation: Speir, R. W. (1961). Effect of Several Inorganic Salts on Infectivity of Mengo Virus. Proceedings of the Society for Experimental Biology and Medicine, 106(2), 402-404. https://doi.org/10.3181/00379727-106-26352
citation: Ramalingam S, Cai B, Wong J, Twomey M, Chen R, Fu RM, Boote T, McCaughan H, Griffiths SJ, Haas JG. Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels. Sci Rep. 2018 Sep 11;8(1):13630. doi: 10.1038/s41598-018-31936-y.
PMID: 30206371
citation: Ramalingam S, Graham C, Dove J, Morrice L, Sheikh A. A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold. Sci Rep. 2019 Jan 31;9(1):1015. doi: 10.1038/s41598-018-37703-3.
PMID: 30705369
citation: Wright FL, Gamboni F, Moore EE, Nydam TL, Mitra S, Silliman CC, Banerjee A. Hyperosmolarity invokes distinct anti-inflammatory mechanisms in pulmonary epithelial cells: evidence from signaling and transcription layers. PLoS One. 2014 Dec 5;9(12):e114129. doi: 10.1371/journal.pone.0114129. eCollection 2014.
PMID: 25479425
citation: Nydam TL, Moore EE, McIntyre RC Jr, Wright FL, Gamboni-Robertson F, Eckels PC, Banerjee A. Hypertonic saline attenuates TNF-alpha-induced NF-kappaB activation in pulmonary epithelial cells. Shock. 2009 May;31(5):466-72. doi: 10.1097/SHK.0b013e31818ec47d.
PMID: 18948845
citation: Gamboni F, Anderson C, Mitra S, Reisz JA, Nemkov T, Dzieciatkowska M, Jones KL, Hansen KC, D'Alessandro A, Banerjee A. Hypertonic Saline Primes Activation of the p53-p21 Signaling Axis in Human Small Airway Epithelial Cells That Prevents Inflammation Induced by Pro-inflammatory Cytokines. J Proteome Res. 2016 Oct 7;15(10):3813-3826. doi: 10.1021/acs.jproteome.6b00602. Epub 2016 Aug 29.
PMID: 27529569
citation: Mitra S, Schiller D, Anderson C, Gamboni F, D'Alessandro A, Kelher M, Silliman CC, Banerjee A, Jones KL. Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. PLoS One. 2017 Dec 18;12(12):e0189536. doi: 10.1371/journal.pone.0189536. eCollection 2017.
PMID: 29253007
citation: Deree J, Martins JO, Leedom A, Lamon B, Putnam J, de Campos T, Hoyt DB, Wolf P, Coimbra R. Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation-induced pulmonary inflammation through attenuation of neutrophil degranulation and proinflammatory mediator synthesis. J Trauma. 2007 Jan;62(1):104-11. doi: 10.1097/TA.0b013e31802d96cb.
PMID: 17215740
citation: Pimentel RN, Petroni RC, Barbeiro HV, Barbeiro DF, Andrade MM, Ariga SK, Soriano FG. Hypertonic solution-induced preconditioning reduces inflammation and mortality rate. J Inflamm (Lond). 2019 Jul 3;16:16. doi: 10.1186/s12950-019-0220-4. eCollection 2019.
PMID: 31312113
citation: Reeves EP, Molloy K, Pohl K, McElvaney NG. Hypertonic saline in treatment of pulmonary disease in cystic fibrosis. ScientificWorldJournal. 2012;2012:465230. doi: 10.1100/2012/465230. Epub 2012 May 3.
PMID: 22645424
citation: Reeves EP, McCarthy C, McElvaney OJ, Vijayan MS, White MM, Dunlea DM, Pohl K, Lacey N, McElvaney NG. Inhaled hypertonic saline for cystic fibrosis: Reviewing the potential evidence for modulation of neutrophil signalling and function. World J Crit Care Med. 2015 Aug 4;4(3):179-91. doi: 10.5492/wjccm.v4.i3.179. eCollection 2015 Aug 4.
PMID: 26261770
citation: Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, Azar A, Baroody FM, Bachert C, Canonica GW, Chacko T, Cingi C, Ciprandi G, Corey J, Cox LS, Creticos PS, Custovic A, Damask C, DeConde A, DelGaudio JM, Ebert CS, Eloy JA, Flanagan CE, Fokkens WJ, Franzese C, Gosepath J, Halderman A, Hamilton RG, Hoffman HJ, Hohlfeld JM, Houser SM, Hwang PH, Incorvaia C, Jarvis D, Khalid AN, Kilpelainen M, Kingdom TT, Krouse H, Larenas-Linnemann D, Laury AM, Lee SE, Levy JM, Luong AU, Marple BF, McCoul ED, McMains KC, Melen E, Mims JW, Moscato G, Mullol J, Nelson HS, Patadia M, Pawankar R, Pfaar O, Platt MP, Reisacher W, Rondon C, Rudmik L, Ryan M, Sastre J, Schlosser RJ, Settipane RA, Sharma HP, Sheikh A, Smith TL, Tantilipikorn P, Tversky JR, Veling MC, Wang Y, Westman M, Wickman M, Zacharek M. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018 Feb;8(2):108-352. doi: 10.1002/alr.22073.
PMID: 29438602
citation: Tarrant BJ, Le Maitre C, Romero L, Steward R, Button BM, Thompson BR, Holland AE. Mucoactive agents for chronic, non-cystic fibrosis lung disease: A systematic review and meta-analysis. Respirology. 2017 Aug;22(6):1084-1092. doi: 10.1111/resp.13047. Epub 2017 Apr 11.
PMID: 28397992
citation: Lin L, Chen Z, Cao Y, Sun G. Normal saline solution nasal-pharyngeal irrigation improves chronic cough associated with allergic rhinitis. Am J Rhinol Allergy. 2017 Mar 1;31(2):96-104. doi: 10.2500/ajra.2017.31.4418.
PMID: 28452705
citation: Liedtke CM. Understanding the cellular mechanism for inhaled hyperosmotic saline therapy for patients with cystic fibrosis. Focus on "Effect of apical hyperosmotic sodium challenge and amiloride on sodium transport in human bronchial epithelial cells from cystic fibrosis donors". Am J Physiol Cell Physiol. 2013 Dec 1;305(11):C1096-7. doi: 10.1152/ajpcell.00250.2013. Epub 2013 Aug 28. No abstract available.
PMID: 23986195
citation: Huiberts A, Zweijpfenning SMH, Pennings LJ, Boeree MJ, van Ingen J, Magis-Escurra C, Hoefsloot W. Outcomes of hypertonic saline inhalation as a treatment modality in nontuberculous mycobacterial pulmonary disease. Eur Respir J. 2019 Jul 11;54(1):1802143. doi: 10.1183/13993003.02143-2018. Print 2019 Jul. No abstract available.
PMID: 31000680
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No