S-Nitrosylation Therapy of COVID-19

Covid19 Clinical Trial

Official title:

Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid-19 Patients Receiving Supplemental Oxygen Support

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04528771
• Other study ID #: STUDY20210599
• Status: Active, not recruiting
• Phase: Early Phase 1
• Start date: August 5, 2021
• Est. completion date: April 30, 2025

Study information

• Verified date: May 2024
• Source: University Hospitals Cleveland Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: April 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• SARS-CoV2 Infection

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
James Reynolds	Case Western Reserve University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Emergent Adverse Events	Adverse events related to SNO therapy.	30 days
Primary	Frequency of Intubation	Number of intubations required.	30 days
Primary	Progression to use of ECMO	Use of ECMO required.	30 days
Secondary	Time to Clinical Status Improvement	Number of days required to see a greater than or equal to 2 point improvement on the WHO 9-point clinical status assessment ordinal scale.; Clinical status will be assessed using the WHO 9-point ordinal scale as follows: 0. Uninfected - no clinical or virological evidence of infection; Ambulatory - no limitation of activities; Ambulatory - Limitation of activities; Hospitalized, mild disease - no oxygen therapy; Hospitalized, mild disease - oxygen by mask or nasal prongs; Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen; Hospitalized, severe disease - intubation and mechanical ventilation; Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO); Dead	30 days
Secondary	Clinical Status	Proportion of patients in each stage at maximum severity on the 9-point clinical status assessment ordinal scale.; Clinical status will be assessed using the WHO 9-point ordinal scale as follows: 0. Uninfected - no clinical or virological evidence of infection; Ambulatory - no limitation of activities; Ambulatory - Limitation of activities; Hospitalized, mild disease - no oxygen therapy; Hospitalized, mild disease - oxygen by mask or nasal prongs; Hospitalized, severe disease - non-invasive ventilation or high-flow oxygen; Hospitalized, severe disease - intubation and mechanical ventilation; Hospitalized, severe disease - ventilation + additional organ support (pressors, RRT, ECMO); Dead	30 days
Secondary	Respiratory Clinical Status	Respiratory clinical status assessed by a 7-point respiratory status ordinal scale that captures oxygen requirement, ventilator support or death.; 7-Point Respiratory Severity Scale Range: 1-7 Higher values = worse; Not receiving oxygen supplementation; AND room air oxygen saturation = 95%; Supplemental oxygen = 2 liters/min; OR room air oxygen saturation = 94%; Supplemental nasal oxygen >2 and <= 5 liters/min; Supplemental nasal oxygen >5 liters/min; HFNC or NIV with FiO2 > 50%; Intubation or ECMO; Death	30 days
Secondary	Duration of Hospitalization	Duration of total hospitalization days as measured by total hospitalization, ventilator and ICU days	30 days
Secondary	All-Cause Mortality	All-cause mortality	30, 60 days
Secondary	Time to Discontinuation of Oxygen Therapy	Number of days required to discontinue oxygen supportive therapy	30 days
Secondary	Discontinuation of Oxygen Therapy	Proportion of patients alive and with discontinued oxygen supportive therapy at day 30	30 days