The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.
Randomized controlled trial for safety of a 6-hour escalating dose of S-nitrosylation therapy
or placebo to ventilated patients. This will be a single-site study conducted within the
UH-CMC medical ICU designated COVID-19 quarantine areas.
Drug: SNO
Six-hour SNO treatment by inhalation at a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr. Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
Drug: Nitrogen gas
Six-hour nitrogen gas treatment by inhalation.Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
Other Name: Placebo
Inclusion Criteria (Severe COVID-19 Status)
- Hospitalized with confirmed SARS-CoV-2 infection by polymerase chain reaction (PCR) or
other validated tests as they become available within 30 days of enrollment.
- In mild respiratory distress, defined as a P/F ratio of between 200 and 325 mm Hg.
- Spontaneously breathing subjects receiving > 4 liters/min of oxygen.
- Patients enrolled and able to start ENO treatment after oxygen stabilization.
- Willing and able to provide written informed consent, or with a legal representative
who can provide informed consent, or enrolled under International Conference on
Harmonization (ICH) E6(R2) 4.8.15 emergency use provisions as deemed necessary by the
investigator (participants ≥ 18 years of age).
- 18-89 years of age
Exclusion Criteria
- COVID-19 patients with mild to no respiratory distress, defined as P/F ratio > 325 mm
Hg.
- COVID-19 patients receiving supplemental oxygen equivalent to an FiO2 of > 0.90
(reduction of FiO2 at this level or higher when ENO is blended into gas source cannot
be avoided).
- COVID-19 patients receiving supplemental oxygen with active ventilatory support, CPAP,
etc.
- 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.
- Subjects with past medical history of lung malignancy or pneumonectomy or lung
transplant
- Subjects who have a history of malignancy or other irreversible disease/conditions
with a 6-month mortality > 50%
- Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes
- Patients on extracorporeal membrane oxygenation (ECMO) + patients intubated on
ventilator
- Patient groups at an increased risk to form methemoglobin. (e.g. congenital variants
of Met-Hb)
- Patients with anemia, defined as a hemoglobin of < 9 g/dL
- Individuals who are pregnant or breastfeeding
- Individuals with an acute disorder or history of chronic diseases of the heart, lungs,
kidney, liver, or any other medical condition that in the opinion of the screening
physician makes them unsuitable for study.
- Individuals taking nitrates.
- Individuals receiving PDE-5 inhibitors, any drugs that are nitric oxide donors (e.g.
prilocaine, sodium nitroprusside and nitroglycerine), drugs known to increase
methemoglobin (e.g. lidocaine, prilocaine, benzocaine, or dapsone), drugs that
interfere with nitrite metabolism (e.g. allopurinol) and drugs that may potentiate
hypotension (e.g. antihypertensives, diuretics, meperidine).
- Individuals with an inherited or acquired blood coagulation disorder, congenital
methemoglobinemia, or a familial hemoglobinopathy that impacts oxygen delivery (e.g.
sickle cell).
- Individuals who might have difficulty with the placement of a face mask (e.g.
claustrophobia, uncontrolled asthma, severe allergies, sensitive skin) and/or the
inhalation of a product for approximately 6 hours.
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Robert Schilz, DO, PhD, Principal Investigator
University Hospitals Cleveland Medical Center