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Nitric Oxide Gas Inhalation for Severe Acute Respiratory Syndrome in COVID-19. (NOSARSCOVID)
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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: NCT04290871 |
Recruitment Status :
Withdrawn
(A new coordinating center has been defined (Massachusetts General Hospital))
First Posted : March 2, 2020
Last Update Posted : March 24, 2020
|
Sponsor:
Xijing Hospital
Collaborators:
Massachusetts General Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Information provided by (Responsible Party):
chonglei, Xijing Hospital
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Study Description
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Brief Summary:
The investigators will enroll 102
patients with a confirmed diagnosis of COVID-19. Patients will be
randomized to receive either inhaled nitric oxide (per protocol) or
placebo. ICU Standards of care will be the institution's own protocols
(such as ventilation strategies and use and dose of antivirals and
antimicrobials, steroids, inotropic and vasopressor agents).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Coronavirus SARS (Severe Acute Respiratory Syndrome) | Drug: Nitric Oxide Gas | Phase 2 |
Detailed Description:
2019-new
Coronavirus (2019-nCoV) infection (COVID-19) is highly contagious and
responsible for thousands of casualties. Originated in Wuhan (China),
the 2019-nCoV is spreading to many countries, including Italy, Korea and
Japan. While no targeted-treatment against 2019-nCoV virus is available
to-date, inhaled nitric oxide gas (NO) has shown antiviral activity
against Coronavirus during the 2003 SARS outbreak. The investigators
designed this study to assess whether inhaled NO improves survival in
patients affected with severe COVID-2019.
The clinical spectrum of
symptomatic patients ranges from mild upper respiratory syndrome to
severe diffuse viral pneumonia in the context of severe multiorgan
dysfunction leading to death. In China, overall reported fatality rate
is between 2.2% in patients with proven infection. In hospitalized
patients with COVID-19, about 25% required admission to ICU. Of these,
61% of patients met clinical criteria for acute respiratory distress
syndrome (ARDS). In another retrospective study in Wuhan (China) on 52
critically ill patients with COVID-19, the incidence of patients with
pneumonia meeting ARDS criteria was 67%. ICU mortality reached 63%, with
various profiles of combined organ failure in deceased patients (81%
with ARDS, 37.5% with AKI, 28% with cardiac injury and 28% with liver
failure).
In 2004, during the
Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) outbreak, it
was demonstrated that treatment with NO reversed pulmonary hypertension,
improved severe hypoxia and shortened the length of ventilatory support
as compared to matched control patients with SARS-CoV. In a subsequent
in-vitro study, NO donors (e.g. S-nitroso-N-acetylpenicillamine) greatly
increased the survival rate of SARS-CoV-infected eukaryotic cells,
suggesting direct antiviral effects of NO. Coronavirus responsible for
SARS-CoV shares most of the genome of COVID-19 indicating potential
effectiveness of inhaled NO therapy in these patients.
Here, the investigators
propose a randomized clinical trial aimed to prevent progression of the
disease in patients with severe acute respiratory syndrome.
Control group: the
institutional standard of care will be delivered. Treatment group: in
addition to standard therapy, the subjects will receive inhalation of
NO. Inspired NO/N2 will be delivered at 80 parts per million (ppm) in
the first 48 hours of enrollment. After that, NO levels will be
decreased to 40 ppm until severe hypoxia resolves. Weaning from NO will
start when patients improves the level of oxygenation to a PaO2/FiO2
> 300 mmHg or SpO2 > 93% for more than 24 hours consecutively.
Physician will follow their own institutional weaning protocols. In the
absence of institutional protocols, NO will be reduced every 4 hours in
step-wise fashion starting from 40 ppm to 20, 10, 5, 3, 2 and 1 ppm. If
hypoxemia (SpO2 < 93%) or acute hypotension (systolic blood pressure
< 90 mmHg) occurs during weaning, NO should be increased to a prior
higher concentration.
Safety: prolonged
treatment with inhaled NO can lead to increased methemoglobin levels.
Blood levels of methemoglobin will be monitored via a non-invasive
CO-oximeter or MetHb levels in blood. If methemoglobin levels rise above
5% at any point of the study, inhaled NO concentration will be halved.
Study Design
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 0 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Nitric Oxide Gas Inhalation Therapy for Severe Acute Respiratory Syndrome Due to COVID-19. |
| Estimated Study Start Date : | March 23, 2020 |
| Estimated Primary Completion Date : | March 1, 2021 |
| Estimated Study Completion Date : | March 1, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Coronavirus Infections
Drug Information available for:
Nitric oxide
Arms and Interventions
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| Arm | Intervention/treatment |
|---|---|
| Experimental: Treatment Group
Nitric Oxide gas will be administered in the ventilatory circuit.
|
Drug: Nitric Oxide Gas
Inspired NO will be
delivered at 80 parts per million (ppm) in the first 48 hours of
enrollment. After that, NO levels will be decreased to 40 ppm until
severe hypoxia resolves. Weaning from NO will start when patients
improves the level of oxygenation to a PaO2/FiO2 > 300 mmHg or SpO2
> 93% for more than 24 hours consecutively. Physician will follow
their own institutional weaning protocols. In the absence of
institutional protocols, NO will be reduced every 4 hours in step-wise
fashion starting from 40 ppm to 20, 10, 5, 3, 2 and 1 ppm.
Other Name: Nitric Oxide inhalation
|
| Sham Comparator: Control Group
The delivery system will be set up anyway without study gas administration
|
Drug: Nitric Oxide Gas
Inspired NO will be
delivered at 80 parts per million (ppm) in the first 48 hours of
enrollment. After that, NO levels will be decreased to 40 ppm until
severe hypoxia resolves. Weaning from NO will start when patients
improves the level of oxygenation to a PaO2/FiO2 > 300 mmHg or SpO2
> 93% for more than 24 hours consecutively. Physician will follow
their own institutional weaning protocols. In the absence of
institutional protocols, NO will be reduced every 4 hours in step-wise
fashion starting from 40 ppm to 20, 10, 5, 3, 2 and 1 ppm.
Other Name: Nitric Oxide inhalation
|
Outcome Measures
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Primary Outcome Measures :
- SARS-free patients at 14 days [ Time Frame: 14 days since beginning of treatment ]Percentage of patients that have a PaO2/FiO2 ratio steadily > 300 in ambient air
Secondary Outcome Measures :
- Survival at 28 days [ Time Frame: 28 days ]
- Survival at 90 days [ Time Frame: 90 days ]
- SARS-free days at 28 days [ Time Frame: 28 days ]Composite outcome in which: Death=0, Days of treatment =1
- SARS -free days at 90 days [ Time Frame: 90 days ]Composite outcome in which: Death=0, Days of treatment =1
- Renal Replacement Therapy [ Time Frame: 28 days ]Incidence
- Liver Failure [ Time Frame: 28 days ]Incidence
- Mechanical Support of Circulation [ Time Frame: 28 days ]Incidence of patients requiring VA-ECMO, LVAD, IABP
- PaO2/FiO2 ratio in ambient air [ Time Frame: daily for 28 days ]In ambient air if possible
Eligibility Criteria
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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.
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.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age ≥18 years
- Laboratory (RT-PCR) confirmed infection with 2019-nCoV
- PaO2/FiO2 < 300 or SpO2 below 93% breathing ambient air
Exclusion Criteria:
- Physician makes a decision that trial involvement is not in the patient's best interest, or any condition that does not allow the protocol to be followed safely
- Pregnant or positive pregnancy test in a pre-dose examination
- Use of high flow nasal cannula
Contacts and Locations
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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): NCT04290871
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): NCT04290871
Sponsors and Collaborators
Xijing Hospital
Massachusetts General Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Investigators
| Principal Investigator: | Chong Lei, MD, PhD | Fourth Military Medical University | |
| Principal Investigator: | Lorenzo Berra, MD | Massachusetts General Hospital |
More Information
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Publications:
| Responsible Party: | chonglei, Chong Lei, MD, PhD, Xijing Hospital |
| ClinicalTrials.gov Identifier: | NCT04290871 History of Changes |
| Other Study ID Numbers: | NO-SARS-COVID-19 |
| First Posted: | March 2, 2020 Key Record Dates |
| Last Update Posted: | March 24, 2020 |
| Last Verified: | March 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Additional relevant MeSH terms:
| Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome Disease Pathologic Processes Respiratory Tract Diseases Coronaviridae Infections Nidovirales Infections RNA Virus Infections Virus Diseases Respiratory Tract Infections 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 |
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