Treatment of Lung Injury From COVID-19 Infection With Intravenous Sodium Nitrite

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Nitrite Injection for treatment of patients infected with COVID-19 who develop lung injury and require mechanical ventilation.

Detailed Description
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This Phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of intravenous Sodium Nitrite Injection for treatment of patients infected with COVID-19 who develop lung injury and require mechanical ventilation. The primary objective is to compare the two treatment groups with respect to the proportion of study subjects who are alive and free of respiratory failure at Day 28.

Official Title
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Treatment of Lung Injury From COVID-19 Infection With Intravenous Sodium Nitrite: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Study

Conditions
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COVID-19, Acute Respiratory Distress Syndrome, Acute Respiratory Failure

Intervention / Treatment
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* Drug: Sodium Nitrite
* Drug: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older; Diagnosed COVID-19 disease with confirmed SARS-coV-2 viral infection; Able to sign the informed consent form (ICF) or next of kin/legal guardian able to sign informed consent; Randomization within 24 hours of intubation and mechanical ventilation due to respiratory failure from COVID-19 infection; Absolute lymphocyte count > 800 / mm3; Women of childbearing potential (WCBP) must have a negative urine or serum (if anuric) pregnancy test at screening; WCBP must agree to abstain from sex or use an adequate method of contraception from the time of informed consent through Day 28; Males must abstain from sex with WCBP or use an adequate method of contraception from the time of informed consent through Day 28. Exclusion Criteria: Methemoglobinemia > 2%; Hypotension with systemic blood pressure < 90/60 mm Hg, or uncontrolled hypotension despite vasopressor support; History of sickle cell disease, thalassemia, G6PD deficiency, lung transplant, or allergy to sodium nitrite; Hemoglobin < 8 gm/dL; Renal impairment with creatinine clearance < 60 mL/min/1.73m2; Treatment within the past 48 hours with allopurinol (a medication that could interfere with nitrite metabolism); Treatment within the past 24 hours with organic nitrates such as nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, sodium nitroprusside, and inhaled nitric oxide; Treatment within the past 24 hours with lidocaine, prilocaine, benzocaine, and dapsone; Requiring extracorporeal membrane oxygenation (ECMO); Subjects with bacterial or fungal infections except for mild cutaneous infections or sinus infections; Subjects who are pregnant or lactating; Any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study; Clinically relevant serious co-morbid medical conditions including, but not limited to, unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled chronic obstructive or chronic restrictive pulmonary disease, active central nervous system (CNS) disease uncontrolled by standard of care, known positive status for human immunodeficiency virus (HIV) (except if HIV subject has undetectable viral load and a CD4 count of ≥ 500 cells/µL), and/or active hepatitis B or C, cirrhosis, or uncontrolled psychiatric illness/social situations that would limit compliance with study requirements; Treatment within 30 days or 5 half-lives of that agent (whichever is shorter) before the first study drug dose using another investigational drug. Notwithstanding, prospective subjects who receive any of the following drugs or treatments before the first study drug dose or during this study may be considered for participation in this study: (1) a commercially available, FDA-approved drug or treatment used off-label for the treatment of COVID-19, or (2) a drug or treatment that has FDA Emergency Use Authorization for the treatment of COVID-19 patients; Moribund or not expected to survive 48 hours.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sodium Nitrite<br>Hope Pharmaceuticals' Sodium Nitrite Injection administered by continuous intravenous infusion. | Drug: Sodium Nitrite<br>* Continuous intravenous infusion of Sodium Nitrite Injection<br>* Other names: Hope Pharmaceuticals Sodium Nitrite Injection USP 30 mg/mL;|
| Placebo Comparator: Placebo<br>0.9% Sodium Chloride Injection, USP (normal saline) administered by continuous intravenous infusion. | Drug: Normal Saline<br>* Continuous intravenous infusion of Normal Saline<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival with Unassisted Breathing | Proportion of study subjects who are alive and free of respiratory failure at Day 28 | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival without Mechanical Ventilation | Number of days alive without mechanical ventilation from start of study through Day 28 | Day 28 | 
| Survival without Intensive Care | Number of days alive and not in the intensive care unit from start of study through Day 28. | Day 28 | 
| Survival without Hospitalization | Number of days alive and not in hospital from start of study through Day 28. | Day 28 | 
| Survival without ECMO | Alive on Day 28 and no use of ECMO therapy any time between start of study and Day 28. | Day 28 | 
| Survival | Alive on Day 28 | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Acute Respiratory Distress Syndrome, Acute Respiratory Failure, ARDS, Respiratory Failure, Intubation, Mechanical Ventilation, Intubated, Mechanical Ventilator, ECMO, Sodium Nitrite, Nitrite, Nitric Oxide