COVID-19Phase 2NO-COVID-19NCT04388683
Inhaled Nitric Oxide for Preventing Progression in COVID-19
A Phase 2 study testing Nitric Oxide in people with COVID-19, run by Tufts Medical Center at 1 site in United States.
Trial summary
This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age > 60 years, type II DM… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- COVID-19
- What is being tested?
- Nitric Oxide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2020to 23 Nov 2020
- Phase
- Phase 2
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-85 years.
- Admitted to the hospital (med-surg or critical care) with dyspnea
- Diagnosis of COVID-19 based on either
- positive nasal or oral pharyngeal swab by PCR, or
- highly probable clinical picture based on clinical and CXR/CT scan
- Requiring oxygen supplementation OR O2 saturation on room air of ≤ 94%
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- At least 2 of the following 4 risk factors for clinical worsening:
- Age >= 60 years
- T2DM or pre-diabetes as evidenced by either treatment with a hypoglycemic agent or any documented HgA1c >= 5.6
- Obesity, based on BMI >= 30 kg/m2
- Hypertension, based on treatment with an antihypertensive medication or systolic or diastolic blood pressure measurement >= 140 or >= 90 mmHg, documented at enrollment or at any time within the prior 6 months.
Who cannot join
- Intubated or prior intubation (during present hospitalization) or anticipated intubation within the subsequent 2 hours.
- Receiving > 5L/min flow nasal O2 to maintain O2sat greater than or equal to 92%
- Using high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV)
- Receiving iNO, a PDE5 inhibitor, oral or intravenous nitrates, nitroprusside, prilocaine, sulfonamides, or riociguat.
- Other major pulmonary, cardiac, such as chronic obstructive lung disease or heart failure, or systemic illness or disease involvement with potential to represent the primary driver for clinical deterioration within the next 3 days.
- History of group 1 pulmonary hypertension.
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- Pregnancy
- Active breast feeding
- Severe chronic kidney disease, either receiving renal replacement therapy or eGFR < 15 ml/min/m2
- Acute kidney injury (AKI), evidenced by acute doubling of serum creatinine within previous 48 hours.
- Clinically relevant spontaneous alteration of mental state
- Inability to provide written informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prevention of COVID-19 Progression Through Early Administration of Inhaled Nitric Oxide.
This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age > 60 years, type II DM, hypertension, and obesity.
Read the detailed description
Primary Objective:
- To investigate the hypothesis that inhaled NO will reduce clinical worsening of hospitalized, high-risk patients with early COVID-19 to progressive systemic de-oxygenation, intubation, or death.
Secondary Objectives:
- To investigate the hypothesis that the beneficial effects of inhaled NO occur coincident with a decrease in systemic inflammation in COVID-19.
This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age > 60 years, type II DM, hypertension, and obesity.
We will perform computerized block randomization (on day zero) with a 2:1 study drug-to-control ratio to receive either open label pulsed inhaled nitric oxide, in addition to standard of care, or standard of care alone. Randomization will be stratified by being in clinical severity stage 1 or stage 2. Randomization will occur in blocks of 6 subjects: 4 iNO and 2 standard of care. Subjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm)
The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 assessments made within 2 hour windows.
The patient will be followed, and clinical stage determined daily, through discharge, death or 28 days post-randomization. Treatment will be given for up to 2 weeks unless patient deteriorates and requires escalation to high flow or intubation or improves and is no longer deemed to need therapy.
The following severity score 3 times daily, based on the level of oxygenation / ventilation support, where the treatment target is 92% <= O2 saturation < 96%
: Scale Title:7-Point Respiratory Severity Scale Scale Range: 0-6 Higher values = worse
Stage Oxygen support
- Not receiving O2 supplementation; AND room air O2 saturation ≥95%
- Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
- Supplemental nasal O2 >2 and <= 5 liters/min
- Supplemental nasal O2 >5 liters/min
- HFNC or NIV with FiO2 > 50%
- Intubation, ECMO, or need to intubate with "Do not intubate" order
- Death
Treatment effect will also be assessed, as a secondary endpoint, via an alternate severity scale, assigned daily from the data accrued, as above, through 14 days post-randomization or discharge.
Data from this pilot study will be used to plan future a larger randomized controlled outcome trial.
- Conditions
- COVID-19
- Being tested
- Nitric Oxide
- Keywords
- COVID-19, Inhaled Nitric Oxide
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitric OxideDrug
Subjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm). The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Will receive study drug treatment. Receives: Drug: Nitric Oxide |
| Control | No intervention | Will receive standard of care. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Average Maximum Disease Severity Assessed Through 28 Days
The clinical disease severity was assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization were those with scores of 1 or 2 (below), and randomization was stratified according to score (1 or 2). Study drug began within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we calculated clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM.
Measured: 28 days
Secondary outcomes (5)
Days to Maximum Clinical Disease Severity Score
The number of days for participants to reach their maximum clinical disease severity score. Severity score assessed by the following table Stage Oxygen support 0 Not receiving O2 supplementation; AND room air O2 saturation ≥95%
- Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
- Supplemental nasal O2 >2 and ≤ 5 liters/min
- Supplemental nasal O2 >5 liters/min
- HFNC or NIV with FiO2 > 50%
- Intubation, ECMO, or need to intubate with "Do not intubate" order
- Death
Measured: 28 days
Days to Maximum Outcome Severity Score
The number of days for patients to reach maximum severity score from randomization. clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM according to the following table:
The following severity score 3 times daily, based on the level of oxygenation / ventilation support, where the treatment target is 92% ≤ O2 saturation < 96%:
Stage Oxygen support 0 Not receiving O2 supplementation; AND room air O2 saturation ≥95%
- Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
- Supplemental nasal O2 >2 and ≤ 5 liters/min
- Supplemental nasal O2 >5 liters/min
- HFNC or NIV with FiO2 > 50%
- Intubation, ECMO, or need to intubate with "Do not intubate" order
- Death HFNC = high-flow nasal cannula; NIV = non-invasive ventilation
Measured: 28 days
Number of Participants in Each Stage at Maximum Severity
Maximum outcome severity score
Measured: 28 days
Length of Hospital Stay
The numbers of days a patient spent in the hospital.
Measured: 28 days
Mortality
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2020
- Study start12 May 2020
- Primary completion23 Nov 2020
- Study completion23 Nov 2020
Why it stopped: Bellerophon requested study to be stopped.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tufts Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bellerophon
- Responsible party
- Sponsor
- Investigators
- Marvin Konstam, MD, Principal investigator, Tufts Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04388683
- Sponsor's protocol ID
- STUDY00000554
- Acronym
- NO-COVID-19
- Status last verified
- Apr 2022
- First submitted
- 13 May 2020
- Last updated
- 19 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Data from this pilot study will be used to plan future a larger randomized controlled outcome trial.
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of COVID-19 Progression Through Early Administration of Inhaled Nitric Oxide.
- ClinicalTrials.gov ID
- NCT04388683
- Acronym / sponsor ID
- NO-COVID-19 / STUDY00000554
- Conditions
- COVID-19
- Keywords
- COVID-19, Inhaled Nitric Oxide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Bellerophon requested study to be stopped.
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Tufts Medical CenterUniversity, hospital or other
- Collaborators
- Bellerophon
- Study start
- 12 May 2020 (actual)
- Primary completion
- 23 Nov 2020 (actual)
- Study completion
- 23 Nov 2020 (actual)
- First posted
- 14 May 2020 (actual)
- Results
- Posted 19 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age > 60 years, type II DM, hypertension, and obesity.
Detailed description
Primary Objective:
- To investigate the hypothesis that inhaled NO will reduce clinical worsening of hospitalized, high-risk patients with early COVID-19 to progressive systemic de-oxygenation, intubation, or death.
Secondary Objectives:
- To investigate the hypothesis that the beneficial effects of inhaled NO occur coincident with a decrease in systemic inflammation in COVID-19.
This is a pilot randomized-controlled (2:1) open label investigation of inhaled NO to prevent progression to more advanced disease in 42 hospitalized patients with COVID-19, at risk for worsening, based on baseline systemic oxygenation and 2 or more of the major risk factors of age > 60 years, type II DM, hypertension, and obesity.
We will perform computerized block randomization (on day zero) with a 2:1 study drug-to-control ratio to receive either open label pulsed inhaled nitric oxide, in addition to standard of care, or standard of care alone. Randomization will be stratified by being in clinical severity stage 1 or stage 2. Randomization will occur in blocks of 6 subjects: 4 iNO and 2 standard of care. Subjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm)
The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 assessments made within 2 hour windows.
The patient will be followed, and clinical stage determined daily, through discharge, death or 28 days post-randomization. Treatment will be given for up to 2 weeks unless patient deteriorates and requires escalation to high flow or intubation or improves and is no longer deemed to need therapy.
The following severity score 3 times daily, based on the level of oxygenation / ventilation support, where the treatment target is 92% <= O2 saturation < 96%
: Scale Title:7-Point Respiratory Severity Scale Scale Range: 0-6 Higher values = worse
Stage Oxygen support
- Not receiving O2 supplementation; AND room air O2 saturation ≥95%
- Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
- Supplemental nasal O2 >2 and <= 5 liters/min
- Supplemental nasal O2 >5 liters/min
- HFNC or NIV with FiO2 > 50%
- Intubation, ECMO, or need to intubate with "Do not intubate" order
- Death
Treatment effect will also be assessed, as a secondary endpoint, via an alternate severity scale, assigned daily from the data accrued, as above, through 14 days post-randomization or discharge.
Data from this pilot study will be used to plan future a larger randomized controlled outcome trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Drug: Nitric OxideWill receive study drug treatment. |
| Control | No intervention | –Will receive standard of care. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18-85 years.
- Admitted to the hospital (med-surg or critical care) with dyspnea
- Diagnosis of COVID-19 based on either
- Requiring oxygen supplementation OR O2 saturation on room air of ≤ 94%
- At least 2 of the following 4 risk factors for clinical worsening:
Key exclusion criteria (12 listed)
- Intubated or prior intubation (during present hospitalization) or anticipated intubation within the subsequent 2 hours.
- Receiving > 5L/min flow nasal O2 to maintain O2sat greater than or equal to 92%
- Using high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV)
- Receiving iNO, a PDE5 inhibitor, oral or intravenous nitrates, nitroprusside, prilocaine, sulfonamides, or riociguat.
- Other major pulmonary, cardiac, such as chronic obstructive lung disease or heart failure, or systemic illness or disease involvement with potential to represent the primary driver for clinical deterioration within the next 3 days.
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 |
|---|---|---|
| Nitric OxideSubjects will receive iNO using the INO pulse device at a dose of 125 mcg/kg IBW/hr (equivalent to approximately 20 ppm). The clinical disease severity will be assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization will be those with scores of 1 or 2 (below), and randomization will be stratified according to score (1 or 2). Study drug will begin within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we will be calculate clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM. | Drug | Intervention |
Primary outcome
Number of Participants With Average Maximum Disease Severity Assessed Through 28 Days
Time frame: 28 days
The clinical disease severity was assessed pre-randomization as the worse of 2 scores measured 2 hours apart. Patients eligible for randomization were those with scores of 1 or 2 (below), and randomization was stratified according to score (1 or 2). Study drug began within 1 hour of randomization. Beginning on the day following randomization ("day 1"), we calculated clinical score, daily, as the average of 3 measurements taken within 2 hour windows centered at 6AM, 2PM, and 10PM.
5 secondary outcomes
Days to Maximum Clinical Disease Severity Score
Time frame: 28 days
Days to Maximum Outcome Severity Score
Time frame: 28 days
Number of Participants in Each Stage at Maximum Severity
Time frame: 28 days
Length of Hospital Stay
Time frame: 28 days
Mortality
Time frame: 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Data from this pilot study will be used to plan future a larger randomized controlled outcome trial.
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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.
Marvin Konstam, MD principal investigator
Tufts Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitric Oxide in people with COVID-19, run by Tufts Medical Center 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 11 inclusion and 12 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 19 Apr 2022. 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. 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?
Yes. Results are posted in the registry (first posted 19 Apr 2022). 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?
Number of Participants With Average Maximum Disease Severity Assessed Through 28 Days (time frame: 28 days). 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 19 Apr 2022.