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Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 89 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Single-site, double-blinded, randomized, placebo controlled trial with a superiority design. The study will randomize 24 patients 1:1 (12 treatment vs 12 control) to either S-nitrosylation therapy or placebo arms.
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
The investigational product will be prepared and dispensed by designated unblinded site personnel at the pharmacy; the investigational product label will indicate the study number but will not indicate the treatment assignment. Any site personnel involved in the administration and assessment of the investigational product will be blinded to subject treatment assignments throughout the study.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
SNO 		12 patients in the S-nitrosylation arm will receive SNO (six-hour treatment with a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr).
  • 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.
Placebo Comparator
Placebo 		12 patients in the placebo arm will receive nitrogen gas (six-hour treatment).
  • 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 names:
    • Placebo

Recruiting Locations

More Details

NCT ID
NCT04528771
Status
Active, not recruiting
Sponsor
James Reynolds

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.