Back to resultsNitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection (NOCOVID)
Primary Purpose
Corona Virus Infection
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
NORS (Nitric Oxide Releasing Solution)
NORS (Nitric Oxide Releasing Solution)
Sponsored by
About this trial
This is an interventional prevention trial for Corona Virus Infection focused on measuring Antiviral, Virucidal, Nitric Oxide
Eligibility Criteria
Prevention Study Inclusion Criteria:
- Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
- Men and Women ≥ 19 years of age unless local laws dictate otherwise;
- English speaking;
- Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.
- Be symptom-free at screening/baseline.
- Work/live in contact with COVID-19 infected patients or scheduled to work in a setting with high likelihood of contact with COVID-19 infected patients.
Prevention Study Exclusion Criteria:
- Prior Tracheostomy;
- Concomitant treatment of respiratory support (involving any form of oxygen therapy);
- Any clinical contraindications, as judged by the attending physician;
- Any symptoms consistent with COVID-19;
- Pregnant;
- Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
- Prior COVID-19 infection.
Treatment Sub study Inclusion Criteria:
- Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
- Men and Women ≥ 19 years of age unless local laws dictate otherwise;
- English speaking;
- Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP;
- Positive COVID-19 test or presentation of clinical symptoms defined as fatigue with either fever >37.2 (oral) and/or a persistent cough.
Treatment Sub Study Exclusion Criteria:
- Prior Tracheostomy;
- Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
- Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
- Pregnant;
- Currently hospitalized for symptoms of COVID-19.
Sites / Locations
- BC Diabetes
- LMC Manna
- Diex Recherche Québec
- Diex Recherche Joliette
- Diex Recherche Sherbrooke
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
No Intervention
Experimental
Other
Arm Label
Prevention - Standard Precautions
Prevention - NORS + Standard Precautions
Treatment Sub-Study
Arm Description
Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols).
Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols) plus daily NORS treatment for 14 days.
Volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. Ten participants can be directly enrolled in the Treatment sub-study. Participants enrolled in the Prevention study who meet the criteria in this section will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.
Outcomes
Primary Outcome Measures
Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19
Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever >37.2 (oral)and/or a persistent cough.
Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19
Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Secondary Outcome Measures
Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19
Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Prevention Study: Measure the tolerability of NORS treatments
Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
Treatment Sub Study: Measure the virucidal effect of NORS Treatments
Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery
Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
Treatment Sub Study: Determine the reduction in clinical symptoms
Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2
Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2
Full Information
NCT ID
NCT04337918
First Posted
April 6, 2020
Last Updated
February 8, 2021
Sponsor
Sanotize Research and Development corp.
Collaborators
The Emmes Company, LLC, Keyrus Life Science
1. Study Identification
Unique Protocol Identification Number
NCT04337918
Brief Title
Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection
Acronym
NOCOVID
Official Title
Multi-Center, Randomized, Controlled, Phase II Clinical Efficacy Study Evaluating Nitric Oxide Releasing Solution Treatment for the Prevention and Treatment of COVID-19 in Healthcare Workers and Individuals at Risk of Infection
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
May 8, 2020 (Actual)
Primary Completion Date
January 31, 2021 (Actual)
Study Completion Date
February 2, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanotize Research and Development corp.
Collaborators
The Emmes Company, LLC, Keyrus Life Science
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a multi-center, randomized, controlled, phase II clinical efficacy study evaluating a novel Nitric Oxide Releasing Solution (NORS) treatment for the prevention and treatment of COVID-19 in healthcare workers at risk of infection. Participants will be enrolled into one of two components of this study. Based on initial swabs/symptoms, volunteers who are COVID-19 negative will be enrolled in the Prevention study and randomized to receive standard institutional precautions or standard institutional precautions + NORS. Those who are COVID-19 positive will be enrolled in the open-label Treatment Sub-Study.
Detailed Description
The novel, human-infecting corona-virus, provisionally named 2019 novel corona virus (2019-nCoV) is a single-strand, positive-sense RNA virus and has a similar receptor-binding domain structure to that of SARS-CoV and MERS-CoV. The virus is transmitted via airborne droplets to the nasal mucosa. Replication occurs locally in the nasal mucosa, in ciliated epithelial cells, over a 3-day incubation period. The mucosal cells are damaged with a resultant inflammatory response similar to the common cold. During this time the virus is shed in nasal secretions causing disease in the lower respiratory tract, potentially causing fatal viral pneumonia.
The literature supports that NO or its derivatives have inhibitory effects on a variety of viral infections. This inhibitory effect was shown to be marked in Interferon (IFN) mediated inhibition manifested by activated macrophage. It was also shown to be correlated with s-nitrosylation of viral proteins such as reductases and proteases.
Based on the genetic similarities between SARS and corona viruses, similar viricidal effects of NO on COVID-19 can be hypothesized.
SaNOtize has developed an innovative approach to provide nitric oxide gas using a formulation called Nitric Oxide Releasing Solution (NORS). This patented solution releases virucidal doses of NO for a sustained period and is effective at rapidly inactivating Influenza A and SARS-CoV-2.
NORS delivered as a gargle (AM), nasal spray (PRN) or as a nasopharyngeal flush (PM) has the potential to decontaminate the upper respiratory tract that could preventing transmission and progression of COVID-19 in Healthcare Workers & Individuals at Risk of Infection.
The randomized Prevention study will investigate the ability of NORS to prevent COVID-19 infection when used prophylactically. The open-label Treatment Sub-Study is expected to be small and will provide pilot data on the possibility of NORS as a treatment for Mild/Moderate COVID-19 infection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection
Keywords
Antiviral, Virucidal, Nitric Oxide
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Multi-center, prospective, randomized, controlled, phase II, parallel group
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
143 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prevention - Standard Precautions
Arm Type
No Intervention
Arm Description
Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols).
Arm Title
Prevention - NORS + Standard Precautions
Arm Type
Experimental
Arm Description
Participants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols) plus daily NORS treatment for 14 days.
Arm Title
Treatment Sub-Study
Arm Type
Other
Arm Description
Volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. Ten participants can be directly enrolled in the Treatment sub-study.
Participants enrolled in the Prevention study who meet the criteria in this section will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.
Intervention Type
Drug
Intervention Name(s)
NORS (Nitric Oxide Releasing Solution)
Other Intervention Name(s)
NOG, NONI, NONS
Intervention Description
NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.
Intervention Type
Drug
Intervention Name(s)
NORS (Nitric Oxide Releasing Solution)
Other Intervention Name(s)
NOG, NONI, NONS
Intervention Description
Up to ten volunteers who are found to be COVID-19 positive during screening will be eligible to enroll in the 21-day Treatment sub-study and receive daily NORS treatment for 14 days. NORS treatment will consist of daily self-administration of three routes; Nitric Oxide Gargle (NOG) every morning, Nitric Oxide Nasophyaryngeal Irrigation (NONI) every evening, and Nitric Oxide Nasal Spray (NONS) up to 5 times per day.
Any participants enrolled in the Prevention study who meet the criteria for the sub study will roll over into the Treatment Sub-Study but must remain in their randomly assigned group.
Primary Outcome Measure Information:
Title
Prevention Study: Measure the effect of NORS on the prevention of COVID-19 infection among health care professionals at risk of exposure to COVID-19
Description
Measure the proportion of subjects with either swab positive COVID-19 or presentation of clinical symptoms as measured by fatigue with either fever >37.2 (oral)and/or a persistent cough.
Time Frame
14 days
Title
Treatment Sub Study: Measure the efficacy of NORS at reducing the progression of COVID- 19
Description
Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Time Frame
21 days
Secondary Outcome Measure Information:
Title
Prevention Study: Measure the effect of NORS on the prevention of progression of COVID- 19
Description
Measure the proportion of participants requiring requiring hospitalization for COVID-19/flu-like symptoms and/or needing oxygen therapy, BIPAP/CPAP, intubation and mechanical ventilation following enrollment.
Time Frame
21 days
Title
Prevention Study: Measure the tolerability of NORS treatments
Description
Measure the tolerability of the NORS treatments as determined by number of adverse events, pain, discomfort or discontinuations of treatment.
Time Frame
21 days
Title
Treatment Sub Study: Measure the virucidal effect of NORS Treatments
Description
Measure the median number of days to negative conversion of SARS-CoV-2 RT-PCR from a nasopharyngeal swabs.
Time Frame
21 days
Title
Treatment Sub Study: Determine effect of NORS on the speed of clinical recovery
Description
Determine the time to clinical recovery in participants with COVID-19 by measuring the median number of days from enrollment to discharge (if admitted), or to normalization of fever (defined as <36.6°C from axillary site, or < 37.2°C from oral site or < 37.8°C from rectal or tympanic site), respiratory rate (< 24 bpm while breathing room air).
Time Frame
21 days
Title
Treatment Sub Study: Determine the reduction in clinical symptoms
Description
Measure the reduction clinical symptoms in participants with COVID- 19 by the magnitude of the change in Modified Jackson Cold Score Diary Score (5-unit change is a substantial clinical benefit).
Time Frame
21 days
Title
Treatment & Sub Study: Determine positive sero-conversion for SARS-CoV-2
Description
Measure the proportion of participants that have a positive sero-conversion for SARS-CoV-2
Time Frame
21 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Prevention Study Inclusion Criteria:
Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
Men and Women ≥ 19 years of age unless local laws dictate otherwise;
English speaking;
Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP.
Be symptom-free at screening/baseline.
Work/live in contact with COVID-19 infected patients or scheduled to work in a setting with high likelihood of contact with COVID-19 infected patients.
Prevention Study Exclusion Criteria:
Prior Tracheostomy;
Concomitant treatment of respiratory support (involving any form of oxygen therapy);
Any clinical contraindications, as judged by the attending physician;
Any symptoms consistent with COVID-19;
Pregnant;
Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
Prior COVID-19 infection.
Treatment Sub study Inclusion Criteria:
Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
Men and Women ≥ 19 years of age unless local laws dictate otherwise;
English speaking;
Must be willing to use an adequate form of contraception (or abstinence) from the time of the first dose with the IMP until after the last dose of IMP;
Positive COVID-19 test or presentation of clinical symptoms defined as fatigue with either fever >37.2 (oral) and/or a persistent cough.
Treatment Sub Study Exclusion Criteria:
Prior Tracheostomy;
Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
Pregnant;
Currently hospitalized for symptoms of COVID-19.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Road, MD
Organizational Affiliation
Private Practice
Official's Role
Principal Investigator
Facility Information:
Facility Name
BC Diabetes
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Y 3W2
Country
Canada
Facility Name
LMC Manna
City
Pointe-Claire
State/Province
Quebec
ZIP/Postal Code
H9R 4S3
Country
Canada
Facility Name
Diex Recherche Québec
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1N 4V3
Country
Canada
Facility Name
Diex Recherche Joliette
City
Saint-Charles-Borromée
State/Province
Quebec
ZIP/Postal Code
J6E 2B4
Country
Canada
Facility Name
Diex Recherche Sherbrooke
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1L 0H8
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
9573217
Citation
Reiss CS, Komatsu T. Does nitric oxide play a critical role in viral infections? J Virol. 1998 Jun;72(6):4547-51. doi: 10.1128/JVI.72.6.4547-4551.1998. No abstract available.
Results Reference
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PubMed Identifier
10791912
Citation
Colasanti M, Persichini T, Venturini G, Ascenzi P. S-nitrosylation of viral proteins: molecular bases for antiviral effect of nitric oxide. IUBMB Life. 1999 Jul;48(1):25-31. doi: 10.1080/713803459.
Results Reference
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26861246
Citation
Deppisch C, Herrmann G, Graepler-Mainka U, Wirtz H, Heyder S, Engel C, Marschal M, Miller CC, Riethmuller J. Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. Infection. 2016 Aug;44(4):513-20. doi: 10.1007/s15010-016-0879-x. Epub 2016 Feb 9.
Results Reference
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PubMed Identifier
23481089
Citation
Miller CC, Hergott CA, Rohan M, Arsenault-Mehta K, Doring G, Mehta S. Inhaled nitric oxide decreases the bacterial load in a rat model of Pseudomonas aeruginosa pneumonia. J Cyst Fibros. 2013 Dec;12(6):817-20. doi: 10.1016/j.jcf.2013.01.008. Epub 2013 Mar 6.
Results Reference
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PubMed Identifier
22520076
Citation
Miller C, Miller M, McMullin B, Regev G, Serghides L, Kain K, Road J, Av-Gay Y. A phase I clinical study of inhaled nitric oxide in healthy adults. J Cyst Fibros. 2012 Jul;11(4):324-31. doi: 10.1016/j.jcf.2012.01.003. Epub 2012 Apr 18.
Results Reference
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PubMed Identifier
16253152
Citation
McMullin BB, Chittock DR, Roscoe DL, Garcha H, Wang L, Miller CC. The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the intensive care unit. Respir Care. 2005 Nov;50(11):1451-6.
Results Reference
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PubMed Identifier
23562771
Citation
Regev-Shoshani G, Vimalanathan S, McMullin B, Road J, Av-Gay Y, Miller C. Gaseous nitric oxide reduces influenza infectivity in vitro. Nitric Oxide. 2013 May 31;31:48-53. doi: 10.1016/j.niox.2013.03.007. Epub 2013 Apr 2.
Results Reference
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Citation
Regev-Shoshani G, McMullin B, Nation N, Church JS, Dorin C, Miller C. Non-inferiority of nitric oxide releasing intranasal spray compared to sub-therapeutic antibiotics to reduce incidence of undifferentiated fever and bovine respiratory disease complex in low to moderate risk beef cattle arriving at a commercial feedlot. Prev Vet Med. 2017 Mar 1;138:162-169. doi: 10.1016/j.prevetmed.2015.04.008. Epub 2015 Apr 20.
Results Reference
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Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection
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