SARS-CoV2 InfectionEarly Phase 1NCT04528771
S-Nitrosylation Therapy of COVID-19
A Early Phase 1 study testing SNO and Nitrogen gas in people with SARS-CoV2 Infection and Covid19, run by James Reynolds at 1 site in United States.
Trial summary
The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- SARS-CoV2 Infection, Covid19
- What is being tested?
- SNO and Nitrogen gas
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Aug 2021to 30 Apr 2025
- Phase
- Early Phase 1
- 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 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Hospitalized with confirmed SARS-CoV-2 infection by polymerase chain reaction (PCR) or other validated tests as they become available within 30 days of enrollment.
- In mild respiratory distress, defined as a P/F ratio of between 200 and 325 mm Hg.
- Spontaneously breathing subjects receiving > 4 liters/min of oxygen.
- Patients enrolled and able to start ENO treatment after oxygen stabilization.
- Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (participants ≥ 18 years of age).
- 18-89 years of age
Who cannot join
- COVID-19 patients with mild to no respiratory distress, defined as P/F ratio > 325 mm Hg.
- COVID-19 patients receiving supplemental oxygen equivalent to an FiO2 of > 0.90 (reduction of FiO2 at this level or higher when ENO is blended into gas source cannot be avoided).
- COVID-19 patients receiving supplemental oxygen with active ventilatory support, CPAP, etc.
- Physician of record opposed to enrolling the patient due to perceived safety concerns; or any condition that does not allow the protocol to be followed safely.
- Subjects with past medical history of lung malignancy or pneumonectomy or lung transplant
- Subjects who have a history of malignancy or other irreversible disease/conditions with a 6-month mortality > 50%
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- Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes
- Patients on extracorporeal membrane oxygenation (ECMO) + patients intubated on ventilator
- Patient groups at an increased risk to form methemoglobin. (e.g. congenital variants of Met-Hb)
- Patients with anemia, defined as a hemoglobin of < 9 g/dL
- Individuals who are pregnant or breastfeeding
- Individuals with an acute disorder or history of chronic diseases of the heart, lungs, kidney, liver, or any other medical condition that in the opinion of the screening physician makes them unsuitable for study.
- Individuals taking nitrates.
- Individuals receiving PDE-5 inhibitors, any drugs that are nitric oxide donors (e.g. prilocaine, sodium nitroprusside and nitroglycerine), drugs known to increase methemoglobin (e.g. lidocaine, prilocaine, benzocaine, or dapsone), drugs that interfere with nitrite metabolism (e.g. allopurinol) and drugs that may potentiate hypotension (e.g. antihypertensives, diuretics, meperidine).
- Individuals with an inherited or acquired blood coagulation disorder, congenital methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g. sickle cell).
- Individuals who might have difficulty with the placement of a face mask (e.g. claustrophobia, uncontrolled asthma, severe allergies, sensitive skin) and/or the inhalation of a product for approximately 6 hours.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
Official title: Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid-19 Patients Receiving Supplemental Oxygen Support
The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
Read the detailed description
Randomized controlled trial for safety of a 6-hour escalating dose of S-nitrosylation therapy or placebo to ventilated patients. This will be a single-site study conducted within the UH-CMC medical ICU designated COVID-19 quarantine areas.
- Conditions
- SARS-CoV2 Infection, Covid19
- Being tested
- SNO, Nitrogen gas
- Keywords
- respiratory distress, respiratory failure
- Medical subject headings
- COVID-19, Dyspnea, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SNODrug
Six-hour SNO treatment by inhalation at a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr. Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
Nitrogen gasDrug
Also called Placebo
Six-hour nitrogen gas treatment by inhalation.Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
| Study group | Role | What they receive |
|---|---|---|
| SNO | Experimental | 12 patients in the S-nitrosylation arm will receive SNO (six-hour treatment with a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr). Receives: Drug: SNO |
| Placebo | Placebo comparator | 12 patients in the placebo arm will receive nitrogen gas (six-hour treatment). Receives: Drug: Nitrogen gas |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Emergent Adverse Events
Adverse events related to SNO therapy.
Measured: 30 days
Frequency of Intubation
Number of intubations required.
Measured: 30 days
Progression to use of ECMO
Use of ECMO required.
Measured: 30 days
Secondary outcomes (7)
Time to Clinical Status Improvement
Number of days required to see a greater than or equal to 2 point improvement on the WHO 9-point clinical status assessment ordinal scale.
Clinical status will be assessed using the WHO 9-point ordinal scale as follows:
- Uninfected - no clinical or virological evidence of infection
- Ambulatory - no limitation of activities
- Ambulatory - Limitation of activities
- Hospitalized, mild disease - no oxygen therapy
- Hospitalized, mild disease - oxygen by mask or nasal prongs
- Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen
- Hospitalized, severe disease - intubation and mechanical ventilation
- Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO)
- Dead
Measured: 30 days
Clinical Status
Proportion of patients in each stage at maximum severity on the 9-point clinical status assessment ordinal scale.
Clinical status will be assessed using the WHO 9-point ordinal scale as follows:
- Uninfected - no clinical or virological evidence of infection
- Ambulatory - no limitation of activities
- Ambulatory - Limitation of activities
- Hospitalized, mild disease - no oxygen therapy
- Hospitalized, mild disease - oxygen by mask or nasal prongs
- Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen
- Hospitalized, severe disease - intubation and mechanical ventilation
- Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO)
- Dead
Measured: 30 days
Respiratory Clinical Status
Respiratory clinical status assessed by a 7-point respiratory status ordinal scale that captures oxygen requirement, ventilator support or death.
7-Point Respiratory Severity Scale Range: 1-7 Higher values = worse
- Not receiving oxygen supplementation; AND room air oxygen saturation ≥ 95%
- Supplemental oxygen ≤ 2 liters/min; OR room air oxygen saturation ≤ 94%
- Supplemental nasal oxygen >2 and <= 5 liters/min
- Supplemental nasal oxygen >5 liters/min
- HFNC or NIV with FiO2 > 50%
- Intubation or ECMO
- Death
Measured: 30 days
Duration of Hospitalization
Duration of total hospitalization days as measured by total hospitalization, ventilator and ICU days
Measured: 30 days
All-Cause Mortality
All-cause mortality
Measured: 30, 60 days
Time to Discontinuation of Oxygen Therapy
Number of days required to discontinue oxygen supportive therapy
Measured: 30 days
Discontinuation of Oxygen Therapy
Proportion of patients alive and with discontinued oxygen supportive therapy at day 30
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2020
- Study start5 Aug 2021
- Primary completion31 Mar 2025 (estimated)
- Study completion30 Apr 2025 (estimated)
Why it stopped: Study delays
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SARS-CoV2 InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Single-site, double-blinded, randomized, placebo controlled trial with a superiority design. The study will randomize 24 patients 1:1 (12 treatment vs 12 control) to either S-nitrosylation therapy or placebo arms.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- James Reynolds
- Sponsor type
- University, hospital or other
- Collaborators
- Case Western Reserve University
- Responsible party
- Sponsor-investigator, James Reynolds, University Hospitals Cleveland Medical Center
- Investigators
- Robert Schilz, DO, PhD, Principal investigator, University Hospitals Cleveland Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04528771
- Sponsor's protocol ID
- STUDY20210599
- Status last verified
- May 2025
- First submitted
- 25 Aug 2020
- Last updated
- 7 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid-19 Patients Receiving Supplemental Oxygen Support
- ClinicalTrials.gov ID
- NCT04528771
- Acronym / sponsor ID
- STUDY20210599
- Conditions
- SARS-CoV2 Infection, Covid19
- Keywords
- respiratory distress, respiratory failure
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study delays
- Enrolment
- 0 participants (actual)
- Lead sponsor
- James ReynoldsUniversity, hospital or other
- Collaborators
- Case Western Reserve University
- Study start
- 5 Aug 2021 (actual)
- Primary completion
- 31 Mar 2025 (estimated)
- Study completion
- 30 Apr 2025 (estimated)
- First posted
- 27 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
Detailed description
Randomized controlled trial for safety of a 6-hour escalating dose of S-nitrosylation therapy or placebo to ventilated patients. This will be a single-site study conducted within the UH-CMC medical ICU designated COVID-19 quarantine areas.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Single-site, double-blinded, randomized, placebo controlled trial with a superiority design. The study will randomize 24 patients 1:1 (12 treatment vs 12 control) to either S-nitrosylation therapy or placebo arms.
| Arm | Type | Receives |
|---|---|---|
| SNO | Experimental | Drug: SNO12 patients in the S-nitrosylation arm will receive SNO (six-hour treatment with a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr). |
| Placebo | Placebo comparator | Drug: Nitrogen gas12 patients in the placebo arm will receive nitrogen gas (six-hour treatment). |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Hospitalized with confirmed SARS-CoV-2 infection by polymerase chain reaction (PCR) or other validated tests as they become available within 30 days of enrollment.
- In mild respiratory distress, defined as a P/F ratio of between 200 and 325 mm Hg.
- Spontaneously breathing subjects receiving > 4 liters/min of oxygen.
- Patients enrolled and able to start ENO treatment after oxygen stabilization.
- Willing and able to provide written informed consent, or with a legal representative who can provide informed consent, or enrolled under International Conference on Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (participants ≥ 18 years of age).
Key exclusion criteria (16 listed)
- COVID-19 patients with mild to no respiratory distress, defined as P/F ratio > 325 mm Hg.
- COVID-19 patients receiving supplemental oxygen equivalent to an FiO2 of > 0.90 (reduction of FiO2 at this level or higher when ENO is blended into gas source cannot be avoided).
- COVID-19 patients receiving supplemental oxygen with active ventilatory support, CPAP, etc.
- Physician of record opposed to enrolling the patient due to perceived safety concerns; or any condition that does not allow the protocol to be followed safely.
- Subjects with past medical history of lung malignancy or pneumonectomy or lung transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SNOSix-hour SNO treatment by inhalation at a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr. Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization. | Drug | SNO |
| Nitrogen gasAlso: PlaceboSix-hour nitrogen gas treatment by inhalation.Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization. | Drug | Placebo |
Primary outcome
Treatment Emergent Adverse Events
Time frame: 30 days
Adverse events related to SNO therapy.
Frequency of Intubation
Time frame: 30 days
Number of intubations required.
Progression to use of ECMO
Time frame: 30 days
Use of ECMO required.
7 secondary outcomes
Time to Clinical Status Improvement
Time frame: 30 days
Clinical Status
Time frame: 30 days
Respiratory Clinical Status
Time frame: 30 days
Duration of Hospitalization
Time frame: 30 days
All-Cause Mortality
Time frame: 30, 60 days
Time to Discontinuation of Oxygen Therapy
Time frame: 30 days
Discontinuation of Oxygen Therapy
Time frame: 30 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Schilz, DO, PhD principal investigator
University Hospitals Cleveland Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing SNO and Nitrogen gas in people with SARS-CoV2 Infection and Covid19, run by James Reynolds at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. 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: withdrawn, as of the sponsor's last update on 7 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. Some participants in this study may receive a placebo. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 was withdrawn before enrolling participants, so there are no results.
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?
Treatment Emergent Adverse Events (time frame: 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 May 2025.