Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inhaled Nitric Oxide for Preventing Progression in COVID-19 (NO-COVID-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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
Sponsor:
Collaborator:
Bellerophon
Information provided by (Responsible Party):
Tufts Medical Center

Brief 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, hypertension, and obesity.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Nitric Oxide Phase 2

Show Show detailed description

Layout table for study information
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
Will receive study drug treatment.
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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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%

    1. Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
    2. Supplemental nasal O2 >2 and ≤ 5 liters/min
    3. Supplemental nasal O2 >5 liters/min
    4. HFNC or NIV with FiO2 > 50%
    5. Intubation, ECMO, or need to intubate with "Do not intubate" order
    6. Death

  2. 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%

    1. Supplemental O2 ≤ 2 liters/min; OR room air O2 saturation ≤ 94%
    2. Supplemental nasal O2 >2 and ≤ 5 liters/min
    3. Supplemental nasal O2 >5 liters/min
    4. HFNC or NIV with FiO2 > 50%
    5. Intubation, ECMO, or need to intubate with "Do not intubate" order
    6. Death HFNC = high-flow nasal cannula; NIV = non-invasive ventilation

  3. Number of Participants in Each Stage at Maximum Severity [ Time Frame: 28 days ]
    Maximum outcome severity score

  4. Length of Hospital Stay [ Time Frame: 28 days ]
    The numbers of days a patient spent in the hospital.

  5. Mortality [ Time Frame: 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18-85 years.
  2. Admitted to the hospital (med-surg or critical care) with dyspnea
  3. Diagnosis of COVID-19 based on either

    1. positive nasal or oral pharyngeal swab by PCR, or
    2. highly probable clinical picture based on clinical and CXR/CT scan
  4. Requiring oxygen supplementation OR O2 saturation on room air of ≤ 94%
  5. At least 2 of the following 4 risk factors for clinical worsening:

    1. Age >= 60 years
    2. T2DM or pre-diabetes as evidenced by either treatment with a hypoglycemic agent or any documented HgA1c >= 5.6
    3. Obesity, based on BMI >= 30 kg/m2
    4. 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:

  1. Intubated or prior intubation (during present hospitalization) or anticipated intubation within the subsequent 2 hours.
  2. Receiving > 5L/min flow nasal O2 to maintain O2sat greater than or equal to 92%
  3. Using high-flow nasal cannula (HFNC) or non-invasive ventilation (NIV)
  4. Receiving iNO, a PDE5 inhibitor, oral or intravenous nitrates, nitroprusside, prilocaine, sulfonamides, or riociguat.
  5. 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.
  6. History of group 1 pulmonary hypertension.
  7. Pregnancy
  8. Active breast feeding
  9. Severe chronic kidney disease, either receiving renal replacement therapy or eGFR < 15 ml/min/m2
  10. Acute kidney injury (AKI), evidenced by acute doubling of serum creatinine within previous 48 hours.
  11. Clinically relevant spontaneous alteration of mental state
  12. Inability to provide written informed consent.

Information from the National Library of Medicine

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


Locations
Layout table for location information
United States, Massachusetts
Tufts Medical Center
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Bellerophon
Investigators
Layout table for investigator information
Principal Investigator: Marvin Konstam, MD Tufts Medical Center
  Study Documents (Full-Text)

Documents provided by Tufts Medical Center:
Informed Consent Form  [PDF] July 24, 2020

Layout table for additonal information
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.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tufts Medical Center:
COVID-19
Inhaled Nitric Oxide
Additional relevant MeSH terms:
Layout table for MeSH terms
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