The scientific community is in search for novel therapies that can help to face theongoing 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. Somepreliminary data on SARS pneumonia suggest that inhaled Nitric Oxide (NO) could havebeneficial effects on SARS-CoV-2 due to the genomic similarities between this twocoronaviruses. In this study we will test whether inhaled NO therapy prevents progressionin 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