Inhaled Nitric Oxide for Preventing Progression in COVID-19 (NO-COVID-19)
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ClinicalTrials.gov Identifier: NCT04388683 |
Recruitment Status :
Terminated
(Bellerophon requested study to be stopped.)
First Posted : May 14, 2020
Results First Posted : April 19, 2022
Last Update Posted : April 19, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
COVID-19 | Drug: Nitric Oxide | Phase 2 |

Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 10 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Prevention of COVID-19 Progression Through Early Administration of Inhaled Nitric Oxide. |
Actual Study Start Date : | May 12, 2020 |
Actual Primary Completion Date : | November 23, 2020 |
Actual Study Completion Date : | November 23, 2020 |

Arm | Intervention/treatment |
---|---|
Experimental: Intervention
Will receive study drug treatment.
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Drug: Nitric Oxide
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. |
No Intervention: Control
Will receive standard of care.
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- 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.
- Days to Maximum Clinical Disease Severity Score [ Time Frame: 28 days ]
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
- Days to Maximum Outcome Severity Score [ Time Frame: 28 days ]
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
- Number of Participants in Each Stage at Maximum Severity [ Time Frame: 28 days ]Maximum outcome severity score
- Length of Hospital Stay [ Time Frame: 28 days ]The numbers of days a patient spent in the hospital.
- Mortality [ Time Frame: 28 days ]

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Ages Eligible for Study: | 18 Years to 85 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age 18-85 years.
- Admitted to the hospital (med-surg or critical care) with dyspnea
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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.
Exclusion Criteria:
- 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.
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04388683
United States, Massachusetts | |
Tufts Medical Center | |
Boston, Massachusetts, United States, 02111 |
Principal Investigator: | Marvin Konstam, MD | Tufts Medical Center |
Documents provided by Tufts Medical Center:
Responsible Party: | Tufts Medical Center |
ClinicalTrials.gov Identifier: | NCT04388683 |
Other Study ID Numbers: |
STUDY00000554 |
First Posted: | May 14, 2020 Key Record Dates |
Results First Posted: | April 19, 2022 |
Last Update Posted: | April 19, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | Data from this pilot study will be used to plan future a larger randomized controlled outcome trial. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
COVID-19 Inhaled Nitric Oxide |
COVID-19 Respiratory Tract Infections Infections Pneumonia, Viral Pneumonia Virus Diseases Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases Nitric Oxide Bronchodilator Agents |
Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Asthmatic Agents Respiratory System Agents Free Radical Scavengers Antioxidants Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Endothelium-Dependent Relaxing Factors Vasodilator Agents Gasotransmitters Protective Agents |