Acute Respiratory Distress Syndrome, Acute Respiratory Failure, COVID-19
Conditions
Keywords
COVID-19, Acute Respiratory Distress Syndrome, Acute Respiratory Failure, ARDS, Respiratory Failure, Intubation, Mechanical Ventilation, Intubated, Mechanical Ventilator, ECMO, Sodium Nitrite, Nitrite, Nitric Oxide
Brief summary
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
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.
Interventions
DRUGSodium Nitrite
Continuous intravenous infusion of Sodium Nitrite Injection
DRUGNormal Saline
Continuous intravenous infusion of Normal Saline
Sponsors
Hope Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older; 2. Diagnosed COVID-19 disease with confirmed SARS-coV-2 viral infection; 3. Able to sign the informed consent form (ICF) or next of kin/legal guardian able to sign informed consent; 4. Randomization within 24 hours of intubation and mechanical ventilation due to respiratory failure from COVID-19 infection; 5. Absolute lymphocyte count \> 800 / mm3; 6. Women of childbearing potential (WCBP) must have a negative urine or serum (if anuric) pregnancy test at screening; 7. WCBP must agree to abstain from sex or use an adequate method of contraception from the time of informed consent through Day 28; 8. 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
1. Methemoglobinemia \> 2%; 2. Hypotension with systemic blood pressure \< 90/60 mm Hg, or uncontrolled hypotension despite vasopressor support; 3. History of sickle cell disease, thalassemia, G6PD deficiency, lung transplant, or allergy to sodium nitrite; 4. Hemoglobin \< 8 gm/dL; 5. Renal impairment with creatinine clearance \< 60 mL/min/1.73m2; 6. Treatment within the past 48 hours with allopurinol (a medication that could interfere with nitrite metabolism); 7. Treatment within the past 24 hours with organic nitrates such as nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, sodium nitroprusside, and inhaled nitric oxide; 8. Treatment within the past 24 hours with lidocaine, prilocaine, benzocaine, and dapsone; 9. Requiring extracorporeal membrane oxygenation (ECMO); 10. Subjects with bacterial or fungal infections except for mild cutaneous infections or sinus infections; 11. Subjects who are pregnant or lactating; 12. Any condition that, in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study; 13. 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; 14. 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; 15. Moribund or not expected to survive 48 hours.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival with Unassisted Breathing | Day 28 | Proportion of study subjects who are alive and free of respiratory failure at Day 28 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival without Intensive Care | Day 28 | Number of days alive and not in the intensive care unit from start of study through Day 28. |
| Survival without Mechanical Ventilation | Day 28 | Number of days alive without mechanical ventilation from start of study through Day 28 |
| Survival without Hospitalization | Day 28 | Number of days alive and not in hospital from start of study through Day 28. |
| Survival without ECMO | Day 28 | Alive on Day 28 and no use of ECMO therapy any time between start of study and Day 28. |
| Survival | Day 28 | Alive on Day 28 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Kidney Status (2) | Day 14 | Creatinine at Day 14 |
| Liver Status | Day 14 | Liver function tests (ALT and AST) at Day 14 |
| Kidney Status (1) | Day 14 | Blood urea nitrogen (BUN) at Day 14 |
| Lung Status | Day 14 | Oxygenation index (PaO2/FIO2) at Day 14 |
Countries
United States
Outcome results
None listed