Investigation of the Efficacy of CARDIO Softgels PLUS Best-standard-of-care in the Recovery of Patients With COVID-19
Condition: COVID; Covid-19
MeSH terms: COVID-19
Study type: Interventional

Summary: 
      Corona virus disease 2019 (COVID-19) is caused by SARS-CoV-2, a plus-sense single-stranded
      RNA virus. 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. The objective of this study is to investigate the safety and efficacy
      of CARDIO supplementation in the recovery of those with COVID-19 infection following the
      guidance from public health by reducing the need for mechanical respiratory support,
      alleviating respiratory symptoms and reducing mortality.
    

Detailed 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 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.
    

Intervention name(s): Best Standard of Care + CARDIO; Best Standard of Care
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Combination of dietary supplement with clinical care; Combination of placebo with clinical care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment