S-Nitrosylation Therapy of COVID-19

NCT04528771 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: STUDY20210599
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV2 Infection; Covid19

Keywords

respiratory distress; respiratory failure

Outcome Measures

Primary Outcomes (3)

• Treatment Emergent Adverse Events

  Adverse events related to SNO therapy.

  30 days

• Frequency of Intubation

  Number of intubations required.

  30 days

• Progression to use of ECMO

  Use of ECMO required.

  30 days

Secondary Outcomes (7)

• Time to Clinical Status Improvement

  30 days

• Clinical Status

  30 days

• Respiratory Clinical Status

  30 days

• Duration of Hospitalization

  30 days

• All-Cause Mortality

  30, 60 days

Study Arms (2)

SNO

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Nitrogen gas

Interventions

SNO 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.

SNO

Nitrogen gas 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.

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• years of age

You may not qualify if:

• 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).

Sponsors & Collaborators

• James Reynolds: lead
• Case Western Reserve University: collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

COVID-19; Dyspnea; Respiratory Insufficiency

Interventions

Nitrogen

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Elements; Inorganic Chemicals; Gases

Study Officials

• Robert Schilz, DO, PhD

  University Hospitals Cleveland Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 25, 2020
• First Posted: August 27, 2020
• Study Start: August 5, 2021
• Primary Completion: March 31, 2025
• Study Completion: April 30, 2025
• Last Updated: May 7, 2025

Record last verified: 2025-05

Locations

US (1)