S-Nitrosylation Therapy of COVID-19

NCT ID: NCT04528771

Last Updated: 2025-05-07

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-05
• Study Completion Date: 2025-04-30

Brief Summary

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.

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.

Conditions

SARS-CoV2 Infection; Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

SNO

Intervention Type: DRUG

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

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

Group Type: PLACEBO_COMPARATOR

Nitrogen gas

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Placebo

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 89 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Western Reserve University

OTHER

Sponsor Role: collaborator

James Reynolds

OTHER

Sponsor Role: lead

Responsible Party

James Reynolds

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Robert Schilz, DO, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center

Locations

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

STUDY20210599

Identifier Type: -

Identifier Source: org_study_id