A Multicenter, Double-blind, Randomized, Placebo-controlled Clinical Trial to Protect Health Workers Against COVID-19 by Using Previfenon® as Chemoprophylaxis During a SARS-CoV-2 Outbreak. The HERD Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 524
- 主要终点
- Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR
研究概览
简要总结
The purpose of this clinical trial is to determine the efficacy of Previfenon® (EGCG) to prevent COVID-19, enhance systemic immunity, and decrease the frequency and intensity of selected symptoms when used as pre-exposure chemoprophylaxis to SARS-CoV-2.
详细描述
Background. Experimental studies have revealed that epigallocatechin-3-galeate (EGCG), a biologically active polyphenol extracted and purified from Camellia Sinensis, may prevent infection by various kinds of viruses, including coronaviruses. Recent double blind, placebo controlled clinical trials, reported up to 75% reduction in the risk of respiratory infection by healthcare workers during an outbreak of H1N1 influenza, simultaneously enhancing systemic immunity by increasing proliferation of ϒδ T cells (28%) and production of IFN-γ (26%). In molecular docking studies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the causal agent of coronavirus disease 2019 outbreak also known as COVID-19) EGCG was identified as a candidate with very high potential for antiviral chemoprophylaxis of COVID-19.
Primary objective: To determine whether Previfenon®, a proprietary formulation of EGCG ≥ 98% purity stabilized with selected excipients, may clinically prevent COVID-19, enhance systemic immunity, decrease the rate for acute respiratory disease, and reduce the frequency and intensity of selected symptoms of COVID-19.
Secondary objective: To determine safety and tolerability of Previfenon® in terms of liver toxicity and frequency of adverse events.
Design. Multicenter randomized double-blind placebo-controlled trial of healthcare workers in treatment by 40 consecutive days as minimum, or a maximum variable time between 60 to 70 days during a SARS-CoV-2 outbreak in Latin American hospitals exposed to clinical care, contact, or circulation of patients with suspected respiratory acute disease caused by SARS-CoV-2 also known as COVID -19.
Sample size: A minimum effect size of 25% (OR = 0.75) is considered; 5% alpha error; 90% power; R = 0.25 for confounders and 20% for loss to follow up. If a conservative event rate of 7.5% in the untreated group is considered, the trial will require 524 participants (262 each group); if the event rate reaches 13.5%, the trial will require 298 participants (149 each group). It is expected to recruit between 100 to 240 subjects per site.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Volunteer healthcare worker with any valid credential of the center
- •25 years old and over
- •Not having been diagnosed with COVID-19
- •A healthy individual as per investigator's judgment or stating stable non-transmissible chronic disease without hospitalization in the last year, without change of medications or addition of medications to treat chronic illnesses in the last 3 months.
- •No pregnancy or breastfeeding
- •Female subjects of childbearing potential using an effective family planning method or surgical sterilization or not sexually active during the study
- •Do not drink more than 300 ml of tea a day
- •Do not take supplements or products containing EGCG during the study
- •Being able to set aside time each day to complete the study questionnaires
- •Being able to read and understand the informed consent form before the study
排除标准
- •Healthcare worker who does not have a valid credential from the center
- •Under 25 years of age
- •Having been diagnosed with a positive rtPCR for COVID-19
- •History of febrile acute respiratory disease within the previous 12 weeks
- •Volunteer with significant alteration from laboratory tests (standard biochemical profile and hemogram) at screening. A significant abnormality will be defined according investigator's medical judgment.
- •Women during pregnancy or breastfeeding
- •Female subjects of childbearing age who are sexually active during the study who do not use an effective method of family planning or do not have surgical sterilization
- •Known allergy to green tea or EGCG
- •Known starch allergy
- •User of any medication or supplement containing EGCG
- •Volunteer using immunosuppressive drugs
- •Autoimmune disease (Lupus, Sjögren or another), liver disease
- •Anemia requiring treatment
- •Having a chronic infectious disease under treatment
研究组 & 干预措施
Previfenon®
Participants will receive coded non-transparent bottles of Previfenon®, each containing 90 EGCG capsules (250 mg per capsule plus excipients) The total EGCG dose per patient will be 750 mg/day (3 capsules) for 40 consecutive days as minimum or a maximum variable time between 60 to 70 days. It will be divided into three daily intakes of one capsule of Previfenon® every 8 hours.
干预措施: Previfenon® (Drug)
Placebo
Participants will receive coded non-transparent bottles of placebo, each containing 90 starch capsules (250 mg plus excipients) under the same dosage, frequency and duration that Previfenon@ arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR
时间窗: The date for censoring a case will be defined as that date when the rtPCR test results positive minus 4 days, with the aim to calculate the time free of clinically defined COVID-19 infection over 40 to 70 days of intervention
A positive case or event of COVID-19 is defined as a patient with acute respiratory illness presenting fever (37.8º C); at least one of the following symptoms: odynophagia, cough, myalgia, or dyspnea; and a specific positive rtPCR test for SARS-CoV-2.
次要结局
- Composite outcome considering symptomatic and asymptomatic cases with positive rtPCR test(Positive cases in each two-weeks examination and to the end of the study over 40 to 70 days of intervention)
- Event of upper and lower airway respiratory infection(Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention)
- Rate of positive cases for IgM and IgG anti-SARS-CoV-2(Positive cases in each two-week examination and to the end of the study over 40 to 70 days of intervention)
- Hospitalization due to any acute respiratory infection(Positive cases in each two-week examination visit and to the end of the study over 40 to 70 days of intervention)
研究者
Elard Koch, PhD
Head of Reserach
MELISA Institute Genomics & Proteomics Research SpA