COVID-19Phase 3COViNOXNCT04421508
A Study to Assess Pulsed Inhaled Nitric Oxide vs Placebo in Subjects With Mild or Moderate COVID-19
A Phase 3 study testing INOpulse in people with COVID-19 and Coronavirus, run by Bellerophon Pulse Technologies at 17 sites in United States.
Trial summary
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19, Coronavirus, Coronavirus Infection
- What is being tested?
- INOpulse
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 191 participants
- Where
- 17 sitesUnited States
- Study dates
- 12 Jul 2020to 22 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent
- At least 18 years old
- Subjects must be hospitalized and have the following:
- proven or high suspicion of SARS-CoV-2 infection and,
- requiring oxygen supplementation defined as:
- SpO2 ≤ 92% regardless of supplemental oxygen (ie on room air or on oxygen), or
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- SpO2 ≥ 92% on supplemental O2 and in the opinion of the Investigator it is not safe to decrease or remove the supplemental oxygen
- require supplemental oxygen of no more than 10 L/minute, and
- radiologic suspected or proven COVID-19 pneumonitis (chest x-ray or CT scan)
- Female subjects must have a negative pregnancy test
- Willing and able to comply with the treatment schedule and study procedures
Who cannot join
- Participating in another clinical trial of an investigational treatment for COVID-19
- Methemoglobin > 3%
- Evidence of severe multi organ failure
- Use of assisted ventilation prior to initiation of iNO
- Pregnancy or positive pregnancy test pre-dose
- Open tracheostomy
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- Chronic use of a nitric oxide donor agent such as nitroglycerin or drugs known to increase methemoglobin such as lidocaine, prilocaine, benzocaine, nitroprusside, isosorbide, or dapsone at screening
- History or clinical evidence of systolic heart failure, left ventricular dysfunction (LVEF <40%)
- Subjects reporting massive hemoptysis associated with the current illness or with radiologically proven pulmonary embolus
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
University of New Mexico Hospital
Albuquerque, New Mexico, 87106
The Lung Research Center (St. Luke's)
Chesterfield, Missouri, 63017
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
INOVA
Falls Church, Virginia, 22042
Houston Methodist
Houston, Texas, 77030
University of Miami Health System
Miami, Florida, 33136
Temple University Hospital
Philadelphia, Pennsylvania, 19140
Banner University Medical Center
Phoenix, Arizona, 85006
St. Francis Medical Center
Richmond, Virginia, 23114
Memorial Regional Medical Center
Richmond, Virginia, 23116
Chippenham Medical Center
Richmond, Virginia, 23225
Pulmonary Associates of Richmond
Richmond, Virginia, 23226
St. Mary's Hospital
Richmond, Virginia, 23226
Johnston-Willis Hospital
Richmond, Virginia, 23235
Kaiser Permanente - Zion Medical Center
San Diego, California, 92120
Kaiser Permanente - San Diego Medical Center
San Diego, California, 92123
Mercy Health St. Vincent Medical Center
Toledo, Ohio, 43608
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.
Read the detailed description
This is a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed iNO compared to placebo in subjects with COVID-19 who are hospitalized and require supplemental oxygen without assisted ventilation. Subjects will be randomized to receive placebo or iNO125 mcg/kg ideal body weight (IBW)/hour 24 hours daily up to 14 days or until resolution or discharge.
- Conditions
- COVID-19, Coronavirus, Coronavirus Infection
- Being tested
- INOpulse, Placebo
- Keywords
- COVID, Sars-CoV-2, iNO, INOpulse, Severe Acute Respiratory Syndrome (SARS) Pneumonia, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV 2, COViNOX, pulsed inhaled nitric oxide, inhaled nitric oxide, portable pulsed inhaled nitric oxide, nitric oxide
- Medical subject headings
- COVID-19, Coronavirus Infections, Severe Acute Respiratory Syndrome, Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INOpulseCombination product
Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
PlaceboCombination product
Subjects will be treated by means of an INOpulse device using an INOpulse nasal cannula.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Nitric Oxide (iNO) | Active comparator | Pulsed inhaled iNO 125 mcg/kg IBW/hour Receives: Combination Product: INOpulse |
| Placebo | Sham comparator | Pulsed inhaled N2, 99.999% gas Receives: Combination Product: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Subjects Who Died or Had Respiratory Failure
The number of subjects who died or had respiratory failure through Day 28
Measured: Through Day 28
Secondary outcomes (8)
Number of Subjects to Recover
Number of subjects to recover, where recover is defined as attaining a NIAID Ordinal score of 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen or 8) Not hospitalized, no limitations on activities sustained through Day 28, or discharge from hospital without re admission for COVID.
Measured: Through Day 28
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measured: Day 7
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measured: Day 14
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
The assessment of clinical status at the first assessment of a study day. The scale is: 1) Death; 2) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 3) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 4) Hospitalized, requiring supplemental oxygen; 5) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 6) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 7) Not hospitalized, limitation on activities and/or requiring home oxygen; 8) Not hospitalized, no limitations on activities.
Measured: Day 28
Number of Subjects Discharged Alive From Hospital
Number of subjects discharged alive from hospital through Day 28
Measured: Through Day 28
Duration of Hospitalization
Duration of Hospitalization through Day 28
Measured: Through Day 28
All Cause Mortality
All cause mortality through Day 28
Measured: Through Day 28
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
Proportion of subjects with a positive RT-PCR result at baseline from a nasopharyngeal swab through Day 28 reported as a proportion of positive or negative RT-PCR testing.
Measured: Through Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start12 Jul 2020
- Primary completion28 Dec 2020
- Study completion22 Jan 2021
Why it stopped: Futility
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19Studies 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
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 191 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bellerophon Pulse Technologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ashika Ahmed, MD, Study director, Bellerophon Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04421508
- Sponsor's protocol ID
- PULSE-CVD19-001
- Acronym
- COViNOX
- Status last verified
- Jan 2023
- First submitted
- 5 Jun 2020
- Last updated
- 21 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- 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 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Pulsed, Inhaled Nitric Oxide (iNO) Versus Placebo in Subjects With Mild or Moderate Coronavirus (COVID-19)
- ClinicalTrials.gov ID
- NCT04421508
- Acronym / sponsor ID
- COViNOX / PULSE-CVD19-001
- Conditions
- COVID-19, Coronavirus, Coronavirus Infection
- Keywords
- COVID, Sars-CoV-2, iNO, INOpulse, Severe Acute Respiratory Syndrome (SARS) Pneumonia, Severe Acute Respiratory Syndrome Coronavirus 2, SARS-CoV 2, COViNOX
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Futility
- Enrolment
- 191 participants (actual)
- Lead sponsor
- Bellerophon Pulse TechnologiesIndustry (pharma, biotech, devices)
- Study start
- 12 Jul 2020 (actual)
- Primary completion
- 28 Dec 2020 (actual)
- Study completion
- 22 Jan 2021 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Posted 1 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed inhaled iNO compared to placebo in subjects with COVID-19.
Detailed description
This is a randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pulsed iNO compared to placebo in subjects with COVID-19 who are hospitalized and require supplemental oxygen without assisted ventilation. Subjects will be randomized to receive placebo or iNO125 mcg/kg ideal body weight (IBW)/hour 24 hours daily up to 14 days or until resolution or discharge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled Nitric Oxide (iNO) | Active comparator | Combination Product: INOpulsePulsed inhaled iNO 125 mcg/kg IBW/hour |
| Placebo | Sham comparator | Combination Product: PlaceboPulsed inhaled N2, 99.999% gas |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed informed consent
- At least 18 years old
- Subjects must be hospitalized and have the following:
- Female subjects must have a negative pregnancy test
- Willing and able to comply with the treatment schedule and study procedures
Key exclusion criteria (9 listed)
- Participating in another clinical trial of an investigational treatment for COVID-19
- Methemoglobin > 3%
- Evidence of severe multi organ failure
- Use of assisted ventilation prior to initiation of iNO
- Pregnancy or positive pregnancy test pre-dose
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 |
|---|---|---|
| INOpulseSubjects will be treated by means of an INOpulse device using an INOpulse nasal cannula. | Combination product | Inhaled Nitric Oxide (iNO) |
| PlaceboSubjects will be treated by means of an INOpulse device using an INOpulse nasal cannula. | Combination product | Placebo |
Primary outcome
The Number of Subjects Who Died or Had Respiratory Failure
Time frame: Through Day 28
The number of subjects who died or had respiratory failure through Day 28
8 secondary outcomes
Number of Subjects to Recover
Time frame: Through Day 28
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Time frame: Day 7
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Time frame: Day 14
Clinical Status Using National Institute of Allergy and Infectious Diseases (NIAID) 8-point Ordinal Scale
Time frame: Day 28
Number of Subjects Discharged Alive From Hospital
Time frame: Through Day 28
Duration of Hospitalization
Time frame: Through Day 28
All Cause Mortality
Time frame: Through Day 28
Difference in Proportion in RT-PCR Results at Discharge by Treatment Group
Time frame: Through Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Ashika Ahmed, MD study director
Bellerophon Therapeutics
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing INOpulse in people with COVID-19 and Coronavirus, run by Bellerophon Pulse Technologies at 17 sites 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 11 inclusion and 9 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: stopped early, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites 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?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
The Number of Subjects Who Died or Had Respiratory Failure (time frame: Through Day 28). 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 21 Feb 2023.