Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation
Severe acute respiratory syndrome (SARS-CoV-2) due to novel Coronavirus (2019-nCoV) related
infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to
refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric
oxide is a selective pulmonary vasodilator gas used as a rescue therapy in refractory
hypoxemia due to acute respiratory distress syndrome (ARDS). In has also shown in-vitro and
clinical evidence that inhaled nitric oxide gas (iNO) has antiviral activity against other
strains of coronavirus.
The primary aim of this study is to determine whether inhaled NO improves oxygenation in
patients with hypoxic SARS-CoV2.
This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients
will be blinded to the treatment.
Intubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection
and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not
(control group). Treatment will be stopped when patients are free from hypoxemia for more
than 24 hours.
Drug: Nitric Oxide Gas
80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop.
Weaning criteria: maintenance of a PaO2/FiO2 ratio >/= 300 for at least 24 hours consecutively.
Inclusion criteria: (1) Adult patients, >/= 18 year-old; (2) Patients admitted to the ICU;
(3) Patients who are intubated and mechanically ventilated; (4) Confirmed diagnosis of
SARS-CoV2 by positive rt-PCR.
Exclusion criteria: (1) Patients intubated for more than 72 hours from initiation of the
treatment gas; (2) Subjects enrolled in another interventional research study; (3)
Physician of record opposed to enrolling the patient due to perceived safety concerns; or
any condition that does not allow the protocol to be followed safely; (4) Subjects with
past medical history of lung malignancy or pneumonectomy or lung transplant; (5) Subjects
receiving a tidal volume < 3 cc/kg of ideal body weight at the time of enrollment; (6)
Subjects with severe burns involving more than 40% of Total Body Surface Area; (7) Subjects
that have experienced cardiac arrest with CPR for longer than 30 minutes; (8) Subjects with
a presumed severe deficit in cerebral function with fixed dilated pupil; (9) Subjects
receiving renal replacement therapy at the time of enrollment; (10) Subjects who have an
impaired ability to ventilate without assistance; (11) Subjects who have a history of
malignancy or other irreversible disease/conditions with a 6-month mortality > 50%; (12)
Subjects not fully committed to full support at the time of enrollment; (13) Subject
receiving inhaled nitric oxide gas prior to enrollment; (14) Subject's hospital admission
unrelated to COVID-19.
University of Alabama
Birmingham, Alabama, United States
Louisiana State University Health Shreveport
Shreveport, Louisiana, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Danderyd Sjukhus AB
Danderyd, Stockholm, Sweden
Lorenzo Berra, MD, Study Director
Massachusetts General Hospital