Clinical trial NCT04528771: S-Nitrosylation Therapy of COVID-19
Official title: Proof of Concept Safety Trial for S-Nitrosylation Therapy to Improve Oxygenation Status in Severe Covid-19 Patients Receiving Supplemental Oxygen Support
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: EARLY_PHASE1
Conditions: SARS-CoV2 Infection
Covid19
Keywords: respiratory distress
respiratory failure
Lead sponsor: University Hospitals Cleveland Medical Center
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
First posted: 2020-08-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility 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.

Primary outcomes:
measure: Treatment Emergent Adverse Events
timeFrame: 30 days
measure: Frequency of Intubation
timeFrame: 30 days
measure: Progression to use of ECMO
timeFrame: 30 days
Secondary outcomes:
measure: Time to Clinical Status Improvement
timeFrame: 30 days
measure: Clinical Status
timeFrame: 30 days
measure: Respiratory Clinical Status
timeFrame: 30 days
measure: Duration of Hospitalization
timeFrame: 30 days
measure: All-Cause Mortality
timeFrame: 30, 60 days
measure: Time to Discontinuation of Oxygen Therapy
timeFrame: 30 days
measure: Discontinuation of Oxygen Therapy
timeFrame: 30 days
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center
name: Robert Schilz, DO, PhD
role: PRINCIPAL_INVESTIGATOR
References: