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

Phase 2

Withdrawn

• Conditions: COVID-19; Acute Respiratory Distress Syndrome; Acute Respiratory Failure
• Interventions: Drug: Sodium Nitrite; Drug: Normal Saline

• Registration Number: NCT04401527
• Lead Sponsor: Hope Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2020-05-21
• Study First Submitted QC: 2020-05-21
• Study First Posted: 2020-05-26
• Study Start: 2020-07-22
• Primary Completion: 2020-08-15
• Study Completion: 2020-08-15
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-11
• Last Update Posted: 2020-09-16

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sodium Nitrite	Sodium Nitrite	Hope Pharmaceuticals' Sodium Nitrite Injection administered by continuous intravenous infusion.
Placebo	Normal Saline	0.9% Sodium Chloride Injection, USP (normal saline) administered by continuous intravenous infusion.

Primary Outcome Measures

Name	Time	Method
Survival with Unassisted Breathing	Day 28	Proportion of study subjects who are alive and free of respiratory failure at Day 28

Secondary Outcome Measures

Name	Time	Method
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
Survival without Mechanical Ventilation	Day 28	Number of days alive without mechanical ventilation from start of study through Day 28
Survival without Intensive Care	Day 28	Number of days alive and not in the intensive care unit from start of study through Day 28.

Trial Locations

Locations (1)

Participating Research Facility; 🇺🇸 Fort Worth, Texas, United States