Investigation of the Efficacy of CARDIO Softgels PLUS Best-standard-of-care in the Recovery of Patients With COVID-19

SARS-CoV-2, a plus-sense single-stranded RNA virus, is the etiologic agent of COVID-19. After an incubation period, which typically lasts for 5-6 days. COVID-19 patients present with a mild illness that lasts for a few days. Common symptoms are reminiscent of the flu, and include fever, dry cough and dyspnea. A large percentage of patients resolve the infection whereas others progress onto adult respiratory distress syndrome (ARDS) which impedes gas exchange between the alveolar space and the bloodstream and creates the need for assisted respiration.

It is estimated that between 5-10% of asthma patients do not respond to steroid-based therapies and require higher doses of medication to achieve control of their disease, or have asthma exacerbations, persistent symptoms and airway obstruction despite greater medication use. These steroid-resistant asthmatics typically have greater morbidity and disproportionately require 50-80% of asthma-related health care costs. The compromised state of the lung in steroid-resistant asthma patients is similar to former smoker patients, for which eosinophil presence in the lung is believed to be a major pro-inflammatory effector cell in the pathogenesis of asthma. Further, in the United States, chronic lung disease (primarily asthma) was the second most prevalent underlying condition in those admitted to hospital for COVID-19 infection in adults ages 18-49.

CARDIO is a safe, natural, salmon oil based, eosinophil effector function (EEF) reducing, softgel formulation. Fish oil, inclusive of salmon oil, or marine-derived omega-3 supplements have been established as cardioprotective. CARDIO has been studied in human clinical studies for the treatment of cardiovascular disease, and as an antioxidant, with an excellent safety record. CARDIO has demonstrated therapeutic potential for the treatment of allergic and inflammatory conditions, particularly those involving eosinophil effector functions. Specifically, CARDIO at 100 ug/ml inhibited eosinophil response to chemoattractant CCL11 in a Shape Change assay; inhibited eosinophil response to chemoattractant CCL11 in an integrin (CD11b) surface upregulation assay; and significantly enhanced apoptosis, in eosinophils sourced from immuno-modulated individuals. Previous studies have shown that fish oil reduces recruitment and infiltration of eosinophils into airways. Among the bioactive components in fish oil, it has been demonstrated that the docosahexaenoic acid (DHA) has an inhibitory effect on proliferation and migration of eosinophils. In vitro and animal dosing studies have been completed for therapeutic dose determination for an accelerated Phase 2 trial application.

Rationale:

Although the exact mechanism of action is unknown, based on in vitro and in vivo studies, it is hypothesized that CARDIO may reduce morbidity and mortality from COVID-19 by protecting respiratory epithelium and alveolar pneumocytes from eosinophil-mediated damage. In light of the mechanism of action outlined above, it is possible that CARDIO could be used as a therapeutic for COVID-19 with the goal of preventing progression into severe disease and in particular in preventing the need of a mechanical ventilation.

Study population:

The population being investigated are hospitalized patients, all with mild to moderate respiratory distress due to COVID-19. Though the age has a reasonably wide range to facilitate recruitment, the exclusions in place provide the required guidance measures to ensure patient safety and address associated comorbidities. Individuals most prone to SARS-CoV-2 and hospitalization as a result of SARS-CoV-2 infection are those with co-morbidities such as older age, cancer, cardiovascular disease and hypertension, type I or II diabetes, chronic obstructive pulmonary disease, obesity and on immunosuppressive treatments. Therefore, participants with the above co-morbidities will comprise the population of interest. However, in this context, each participant will be assessed on a case-by-case basis by the Qualified Investigator to ensure all inclusions and none of the exclusions are met, and that the safety of their participation in the study is critically evaluated. The requirement of mild to moderate COVID-19 will be assessed using the most up- to-date National Institutes of Health (NIH) Treatment Guidelines for the Clinical Presentation of People with SARS-CoV-2 Infection. Using the NIH guidelines for clinical presentation of COVID-19 and identification of mild and moderate disease severity will ensure potential patients are evaluated based on the most up-to-date information in the ever changing COVID-19 research landscape. The safety of patients will be assessed at each assessment day, a Data and Safety Monitoring Board will be established, and an interim analysis is planned to guide safe continuation of the study.

The objectives of this randomized, open-label study is to investigate the safety and efficacy of CARDIO plus best standard-of-care in reducing the need for mechanical respiratory support, alleviating respiratory symptoms and reducing mortality in patients with COVID-19 infection in patients who are hospitalized. The SPIRIT statement for protocols items for trials are followed and the reporting will be done in accordance with the Consolidated Standards of Reporting Trials (CONSORT) Statement.