A Randomized, Open-label, Parallel Study to Investigate the Efficacy of CARDIO Softgels PLUS Best-standard-of-care in the Recovery of Patients With COVID-19 Who Are Hospitalized as Well as Patients Following the Guidance From Public Health
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 16
- 主要终点
- Proportion of patients requiring mechanical ventilator until end of study (Day 28)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with signs and symptoms corresponding to COVID-19 viral infection and:
- •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
- •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
- •Males and females between 18 and 75 years of age, inclusive
- •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
- •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
- •Willingness to complete assessments, questionnaires and records associated with the study
- •Provided voluntary, written, informed consent to participate in the study
排除标准
- •Women who are pregnant, breast feeding, or planning to become pregnant during the study
- •Inability to take medications orally
- •Individuals with a known fish allergy or hypersensitivity reaction
- •Individuals with uncontrolled hypotension (systolic blood pressure < 90 mmHg) or need for vasopressor/inotropic medication
- •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)
- •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.
结局指标
主要结局
Proportion of patients requiring mechanical ventilator until end of study (Day 28)
时间窗: Day 28
Proportion of patients requiring mechanical ventilator until end-of-study, when comparing Best Standard of Care treatment (BSC) plus CARDIO unrefined salmon oil vs. BSC alone
次要结局
- Clinical improvement(Day 10, Day 14, Day 28, or Day of discharge)
- Oxygenation requirements assessed by oxygen saturation rates based on number of oxygenation free days during hospital stay(During hospital stay, on day of discharge if prior to Day 28, and on Day 28)
- Oxygenation requirements assessed by oxygen saturation rates based on incidence of new oxygen use, non-invasive ventilation or high flow oxygen devices(During hospital stay, on day of discharge if prior to Day 28, and on Day 28)
- The number of days from hospital admission to hospital discharge(Up to Day 28)
- Temperature measurements after discharge and to end of study (Day 28)(Day 28 and after discharge)
- Time to improvement in oxygenation for at least 48 hours(Day 28 or Day of discharge)
- Duration of mechanical ventilator use until end-of-study (Day 28)(Day 28)
- COVID-19 QoL measurements after discharge and to end of study (Day 28)(Day 28 and after discharge)
- Clinical status(Day 10, Day 14, Day 28, or Day of discharge)
- Time to clinical recovery(Day 28 or Day of discharge)
- Quality of life (QoL)(Day 0, Day 10, Day 14, and Day 28)
- All-cause mortality(Day 28)
- The number of days in intensive care unit (ICU) at Day 28 or day of discharge(Day 28 or Day of discharge)
- Oxygen saturation measurements after discharge and to end of study (Day 28)(Day 28 and after discharge)
- Oxygenation requirements assessed by oxygen saturation rates based on duration of new oxygen use, non-invasive ventilation or high flow oxygen devices(During hospital stay, on day of discharge if prior to Day 28, and on Day 28)
- Serial chest CT or X-ray findings(Day 10 and Day 28 or Day of discharge)
- The total number of days on ventilator at Day 28 or day of discharge(Day 28 or Day of discharge)