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.
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.
Dietary Supplement: Best Standard of Care + CARDIO
Combination of dietary supplement with clinical care
Dietary Supplement: Best Standard of Care
Combination of placebo with clinical care
Inclusion Criteria:
1. Patients with signs and symptoms corresponding to COVID-19 viral infection and:
2. Admitted to hospital and who have been initiated with BSC treatment with mild to
moderate disease as defined by the National Institutes of Health (NIH) Treatment
Guidelines
3. Confirmation of COVID-19 infection This will be assessed by secondary laboratory
confirmation of SARS-CoV-2 infection by reverse-transcription polymerase chain
reaction (RT-PCR) or comparable methodology used by the hospital from any diagnostic
sampling - source for analysis and recovery
4. Males and females between 18 and 75 years of age, inclusive
5. Female patient is not of child-bearing potential, defined as females who have
undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy,
bilateral tubal ligation, complete endometrial ablation) or have been post-menopausal
for at least 1 year prior to screening
Or,
Females of child-bearing potential must have a negative urine pregnancy test and agree
to use a medically approved method of birth control for the duration of the study. All
hormonal birth control must have been in use for a minimum of three months. Acceptable
methods of birth control include:
- Hormonal contraceptives including oral contraceptives, hormone birth control
patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable
contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)
- Double-barrier method
- Intrauterine devices
- Non-heterosexual lifestyle or agrees to use contraception if planning on changing
to heterosexual partner(s)
- Vasectomy of partner at least 6 months prior to screening
6. Willingness to complete assessments, questionnaires and records associated with the
study
7. Provided voluntary, written, informed consent to participate in the study
Exclusion Criteria:
1. Women who are pregnant, breast feeding, or planning to become pregnant during the
study
2. Inability to take medications orally
3. Individuals with a known fish allergy or hypersensitivity reaction
4. Individuals with uncontrolled hypotension (systolic blood pressure < 90 mmHg) or need
for vasopressor/inotropic medication
5. Individuals with renal impairment This will be assessed by increase of creatinine by
50% from baseline, glomerular filtration rate reduction by >25% from baseline or urine
output of <0.5 ml/kg for 6 hours)
6. Individuals with gastrointestinal symptoms that require hospitalization (e.g. severe
nausea, vomiting, diarrhea or/and abdominal pain) Any other condition, that, in the
opinion of the QI, may adversely affect the patient's ability to complete the study or
its measures or pose significant risk to the patient.
Hospital Universitario Cassiano Antonio de Morais
Vitória, Espírito Santo, Brazil
- Instituto de Pesquisa Clínica de Campinas
Campinas, Brazil
Instituto Santa Marta de Ensino e Pesquisa
Taguatinga, Brazil
KGK Science Inc.
London, Ontario, Canada
Markhot Ferenc Oktatókórház és Rendelőintézet, Eger
Eger, Hungary
Albert Schweitzer Kórház-Rendelőintézet, Hatvan
Hatvan, Hungary
The American British Cowdray Medical Center I.A.P.
Ciudad de México, Mexico
General Hospital Paracin
Paracin, Serbia
David Crowley, MD, Principal Investigator
KGK Science Inc.