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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04388683
Recruitment Status : Recruiting
First Posted : May 14, 2020
Last Update Posted : May 18, 2020
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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 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
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : July 31, 2021

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. Prevention of progressive systemic de-oxygenation, with escalation to higher levels of oxygen and ventilatory support or death, assessed using a 7-point severity scale. [ Time Frame: 28 days ]
    Prevention of progressive systemic de-oxygenation, with escalation to higher levels of oxygen and ventilatory support or death, assessed using a 7-point severity scale (See statistical methods). Between-group differences in the average maximum disease severity assessed through 28 days, through the following severity scores: a) increased liter oxygen flow, through a high flow nasal cannula; b) non-invasive ventilation; c) intubation or institution of ECMO; or d) death.


Secondary Outcome Measures :
  1. Prevention of progression assessed by an alternate severity scale [ Time Frame: 28 days ]
  2. Time to reaching maximal severity score [ Time Frame: 28 days ]
  3. Proportion of patients in each stage at maximum severity [ Time Frame: 28 days ]
  4. PaO2/FIO2 or SaO2/FIO2 ratio, measured daily [ Time Frame: 28 days ]
  5. Length of hospital Stay (death assigned as worst case) [ Time Frame: 28 days ]
  6. Frequency of Intubation, ECMO, or need to intubate with "Do Not Resuscitate" order [ Time Frame: 28 days ]
  7. Mortality [ Time Frame: 28 days ]
  8. IL6 level [ Time Frame: 7 days ]
  9. TNF-alpha level [ Time Frame: 7 days ]
  10. Fibrinogen level [ Time Frame: 7 days ]
  11. CRP level [ Time Frame: 7 days ]
  12. Ferritin Level [ Time Frame: 7 days ]
  13. D-dimer level [ Time Frame: 7 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.


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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
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


Contacts
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Contact: Marvin Konstam, MD 617-636-6293 mkonstam@tuftsmedicalcenter.org
Contact: Nicholas Hill, MD 617-636-4288 nhill@tuftsmedicalcenter.org

Locations
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United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Marvin Konstam, MD    617-636-6293    mkonstam@tuftsmedicalcenter.org   
Sponsors and Collaborators
Tufts Medical Center
Bellerophon
Investigators
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Principal Investigator: Marvin Konstam, MD Tufts Medical Center
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Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT04388683    
Other Study ID Numbers: STUDY00000554
First Posted: May 14, 2020    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: May 2020
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.

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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:
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Respiratory Aspiration
Pathologic Processes
Respiration Disorders
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