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Corona Virus InfectionPhase 2NOCOVIDNCT04337918

Nitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection

A Phase 2 study testing NORS (Nitric Oxide Releasing Solution) in people with Corona Virus Infection, run by Sanotize Research and Development corp. at 5 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and olderHealthy volunteers can take part
Conditions the study is for
Corona Virus Infection
What is being tested?
NORS (Nitric Oxide Releasing Solution)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
143 participants
Where
5 sitesCanada
Study dates
8 May 2020to 2 Feb 2021
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Prevention Study Inclusion Criteria:

  1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
  2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
  3. English speaking;
  4. 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.
  5. Be symptom-free at screening/baseline.
  6. 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:

  1. Prior Tracheostomy;
  2. Concomitant treatment of respiratory support (involving any form of oxygen therapy);
  3. Any clinical contraindications, as judged by the attending physician;
  4. Any symptoms consistent with COVID-19;
  5. Pregnant;
  6. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
  7. Prior COVID-19 infection.

Treatment Sub study Inclusion Criteria:

  1. Capable of understanding and providing signed informed consent and ability to adhere to the requirements and restrictions of this protocol;
  2. Men and Women ≥ 19 years of age unless local laws dictate otherwise;
  3. English speaking;
  4. 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;
  5. 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:

  1. Prior Tracheostomy;
  2. Concomitant treatment of respiratory support (involving any form of oxygen therapy); Any clinical contraindications, as judged by the attending physician;
  3. Mentally or neurologically disabled patients who are considered not fit to consent to their participation in the study;
  4. Pregnant;
  5. Currently hospitalized for symptoms of COVID-19.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites

  • LMC Manna

    Pointe-Claire, Quebec, H9R 4S3

  • Diex Recherche Québec

    Québec, Quebec, G1N 4V3

  • Diex Recherche Joliette

    Saint-Charles-Borromée, Quebec, J6E 2B4

  • Diex Recherche Sherbrooke

    Sherbrooke, Quebec, J1L 0H8

  • BC Diabetes

    Vancouver, British Columbia, V5Y 3W2

Other trials in Canada

About this study

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

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.

Read the 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.

Being tested
NORS (Nitric Oxide Releasing Solution)
Keywords
Antiviral, Virucidal, Nitric Oxide
Medical subject headings
Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NORS (Nitric Oxide Releasing Solution)Drug

    Also called NOG, NONI, NONS

    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.

  • NORS (Nitric Oxide Releasing Solution)Drug

    Also called NOG, NONI, NONS

    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.

Study groups in NCT04337918
Study groupRoleWhat they receive
Prevention - Standard PrecautionsNo interventionParticipants COVID-19 negative at baseline will be randomized to receive standard COVID-19 screening and protection (per their facility or organization's protocols).
Prevention - NORS + Standard PrecautionsExperimentalParticipants 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.
Receives: Drug: NORS (Nitric Oxide Releasing Solution)
Treatment Sub-StudyOtherVolunteers 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.
Receives: Drug: NORS (Nitric Oxide Releasing Solution)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 14 days

  2. 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.

    Measured: 21 days

Secondary outcomes (6)

  1. 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.

    Measured: 21 days

  2. 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.

    Measured: 21 days

  3. 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.

    Measured: 21 days

  4. 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).

    Measured: 21 days

  5. 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).

    Measured: 21 days

  6. 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

    Measured: 21 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2020
  2. Study start8 May 2020
  3. Primary completion31 Jan 2021
  4. Study completion2 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multi-center, prospective, randomized, controlled, phase II, parallel group
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
143 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04337918
Sponsor's protocol ID
COVID-CTP-01
Acronym
NOCOVID
Status last verified
Feb 2021
First submitted
6 Apr 2020
Last updated
10 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 9573217

  • 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.

    PubMed 10791912

  • 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.

    PubMed 26861246

  • 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.

    PubMed 23481089

  • 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.

    PubMed 22520076

  • 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.

    PubMed 16253152

  • 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.

    PubMed 23562771

  • 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.

    PubMed 25975664

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NORS (Nitric Oxide Releasing Solution) in people with Corona Virus Infection, run by Sanotize Research and Development corp. at 5 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04337918, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2021.

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