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

Summary

Participation Requirements

Description

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 an...

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. Acute eosinophilic pneumonia (AEP) is an acute respiratory illness of varying severity that includes presentation as ARDS with fatal outcomes. AEP pathology results from an uncontrolled inflammatory response characterized by excessive recruitment of lung eosinophils and production of inflammatory cytokines. Former smokers are at a particularly high risk for developing ARDS and constitute a disproportionately higher burden for scarce intensive care unit (ICU) beds. At first glance, several studies from China and the US CDC show a low smoker prevalence among hospitalized COVID-19 patients. However, parsing of the smoker subset for example from the CDC, shows that former smokers actually constitute a significantly higher percentage of patients moving from "Hospitalized non-ICU" to "Hospitalized ICU" status (73%) as compared to other single underlying condition (44%) patients, and a much higher percentage than Current Smokers (22%). Possible explanations for former smokers being at much greater risk of ARDS disease progression than current smokers include: The continued presence of nicotine in current smokers and its known anti-inflammatory protection Ongoing smoking down-regulates angiotensin converting enzyme 2 (ACE2), which the SARS-CoV-2 uses to invade host cells. In inflamed airways due to allergy or infection, cigarette smoke significantly attenuates inflammatory eosinophilia, eosinophil trafficking and activation of B cells in the bronchoalveolar lavage. Changes in smoking pattern triggers interstitial injury patterns mediated via recruitment and inappropriate persistence of myeloid and other immune cells, including eosinophils, especially after cessation of smoking. The adjacent image shows a Computed Tomographic (CT) of the lungs of a former smoker 2 weeks after resuming smoking following several years of abstinence. It is surprisingly similar in presenting the same bilateral patchy ground-glass opacities seen in COVID-19 patients. Uncontrolled eosinophil production in lung epithelial cells plays a critical role in the destruction of the respiratory epithelium and rapid development of ARDS, particularly in former smoker patients. The pulmonary inflammation leads to cardiac impairment and intravascular coagulation, kidney insufficiency and liver damage. The scope, intensity and rapidity of the host COVID-19 response in former smoker patients strongly advocates for a therapeutic strategy that aims to prevent rather than reverse progression from mild to severe disease. 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. Similar to former smoker patients, 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. In vitro and animal dosing studies have been completed for therapeutic dose determination for an accelerated Phase 2 trial application. It is hypothesized that CARDIO may reduce morbidity and mortality in former smoker patients 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, particularly in former smoker patients with mild illness, with the goal of preventing progression into severe disease. The population being investigated are patients who are not eligible for hospital admittance and are at home following the guidance from public health, 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. 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 following the guidance from public health.

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