The scientific community is in search for novel therapies that can help to face the ongoing epidemics of novel Coronavirus (SARS-Cov-2) originated in China in December 2019. At present, there are no proven interventions to prevent progression of the disease. Some preliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could have beneficial effects on SARS-CoV-2 due to the genomic similarities between this two coronaviruses. In this study we will test whether inhaled NO therapy prevents progression in patients with mild to moderate COVID-19 disease.
To date, no targeted therapeutic treatments for the ongoing COVID-19 outbreak have been
identified. Antiviral combined with adjuvant therapies are currently under investigation. The
clinical spectrum of the infection is wide, ranging from mild signs of upper respiratory
tract infection to severe pneumonia and death.
In the patients who progress, the time period from symptoms onset to development of dyspnea
is reported to be between 5 to 10 days, and that one to severe respiratory distress syndrome
from 10 to 14 days. Globally, 15 to 18% of patients deteriorates to the need of mechanical
ventilation, despite the use of non-invasive ventilatory support in the earliest phases of
the disease. Probability of progression to end stage disease is unpredictable, with the
majority of these patients dying from multi-organ failure. Preventing progression in
spontaneously breathing patients with mild to moderate disease would translate in improved
morbidity and mortality and in a lower use of limited healthcare resources.
In 2004, during the SARS-coronavirus (SARS-CoV) outbreak, a pilot study showed that low dose
( max 30 ppm) inhaled NO for 3 days was able to shorten the time of ventilatory support. At
the same time, NO donor compound S-nitroso-N-acetylpenicillamine increased survival rate in
an in-vitro model of SARS-CoV infected epithelial cells.Based on the genetic similarities
between the two viruses, similar effects of NO on SARS-CoV-2 can be hypothesized. While
further in-vitro testing is recommended, we proposed a randomized clinical trial to test the
effectiveness of inhaled NO in preventing the progression of SARS-CoV-2 related disease, when
administered at an early stage.
Drug: Nitric Oxide
Nitric Oxide (NO) will be delivered together with the standard of care for a period of 20-30 minutes 2 times per day for 14 consecutive days from time of enrollment. Targeted No inhaled concentration will be maintained between 140 and 180 ppm. The gas will be delivered through a CPAP circuit ensuring an end-expiratory pressure between 2 and 10 cmH2O or through a non-rebreathing mask without positive end-expiratory pressure, depending on the clinical needs of the subject.
Other Name: Nitric Oxide inhalation
Inclusion Criteria:
1. Laboratory confirmed COVID19 infection defined with a positive RT-PCR from any
specimen and/or detection of SARS-CoV-2 IgM/IgG antibodies.
2. Hospital admission with at least one of the following:
1. fever ≥ 36.6 °C from axillary site; or ≥ 37.2°C from oral site; or ≥ 37.6°C from
tympanic or rectal site.
2. Respiratory rate ≥ 24 bpm
3. cough
3. Spontaneous breathing with or without hypoxia of any degree. Gas exchange and
ventilation maybe assisted by any continuous continuous airway pressure (CPAP), or any
system of Non Invasive Ventilation (NIV), with Positive End-Expiratory Pressure (PEEP)
≤ 10 cmH2O.
Exclusion Criteria:
1. Tracheostomy
2. Therapy with high flow nasal cannula
3. Any clinical contraindications, as judged by the attending physician
4. Patients enrolled in another interventional study
5. Hospitalized and confirmed diagnosis of COVID-19 for more than 72 hours
6. Previous intubation for COVID-19
7. Patient not committed to full support (DNR, DNI or CMO)
8. Patient requiring oxygen at home for lung comorbidities
9. Primary cause of hopitalization not due to COVID-19
Providence HealthCare Network
Anchorage, Alaska, United States
Louisiana State University Health Shreveport
Shreveport, Louisiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Lorenzo Berra, MD, Principal Investigator
Massachusetts General Hospital