S-Nitrosylation Therapy of COVID-19

James Reynolds

Status and phase: Withdrawn; Early Phase 1

Conditions: SARS-CoV2 Infection; Covid19

Treatments: Drug: Nitrogen gas; Drug: SNO

Study type: Interventional

Funder types: Other

Identifiers

NCT04528771

STUDY20210599

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

SNO

Experimental group

Description:

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).

Treatment:

Drug: SNO

Placebo

Placebo Comparator group

Description:

12 patients in the placebo arm will receive nitrogen gas (six-hour treatment).

Treatment:

Drug: Nitrogen gas