Previfenon® as Chemoprophylaxis of COVID-19 in Health Workers (HERD)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04446065 |
Recruitment Status :
Not yet recruiting
First Posted : June 24, 2020
Last Update Posted : September 9, 2020
|
Tracking Information | |||||||||
---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | June 23, 2020 | ||||||||
First Posted Date ICMJE | June 24, 2020 | ||||||||
Last Update Posted Date | September 9, 2020 | ||||||||
Estimated Study Start Date ICMJE | September 30, 2020 | ||||||||
Estimated Primary Completion Date | September 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
Event of clinical acute respiratory disease with a diagnosis of COVID-19 confirmed with rtPCR [ Time Frame: 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.
|
||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures |
|
||||||||
Original Other Pre-specified Outcome Measures | Same as current | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Previfenon® as Chemoprophylaxis of COVID-19 in Health Workers | ||||||||
Official Title ICMJE | 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 | ||||||||
Brief Summary | 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. | ||||||||
Detailed Description | 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. Intervention. The treatment group will receive 3 capsules of Previfenon® daily containing 250 mg of EGCG one every 8 hours. The control group will receive 3 placebo capsules (starch 250 mg) under the same frequency. Outcomes. The primary outcome will be the rate of clinically defined COVID-19 confirmed with rt-PCR for SARS-CoV-2 viral RNA. Secondary outcomes will be (1) rate of positive cases for IgM or IgG anti-SARS-CoV-2 as measured by a rapid immuno-chromatographic test; (2) rate of positive cases for rtPCR for SARS-Cov-2 viral RNA (3) rate of hospitalization for acute respiratory disease; (4) total rate of lower or upper acute respiratory disease. Exploratory outcomes will be the frequency and intensity of selected symptoms for COVID-19. Safety outcomes will be the number of events of major hepatic toxicity accounted by an increment in liver enzymes and frequency of adverse events during the treatment. Analysis. Comparison of frequencies, means, and proportions for all relevant variables between treated group and placebo will be performed. An interim analysis will be conducted with the first 366 subjects with at least 20 days of treatment during the outbreak. It will be utilized logistic regression to explore the ongoing effect size in a fixed-effect model. Disease-free person-days curves over the total follow up period will be analyzed using Kaplan-Meier and the total effect size will be computed by Cox proportional hazards multiple regression. Leading hypothesis: The use of Previfenon® will have a high efficacy in the chemoprophylaxis of COVID-19 through multiple complementary mechanisms, which ultimately prevent an efficient incubation of the SARS-CoV-2 in the host cells, and simultaneously, enhances systemic immunity against the pathogen. |
||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 2 Phase 3 |
||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: The study will use 2 parallel groups in each center to compare the effects of an oral formulation of EGCG (Previfenon®, patent pending) with those of placebo (starch) in the prevention of respiratory disease caused by SARS-CoV-2 (COVID-19) in health care workers directly exposed to clinical care, daily contact, or traffic of individuals with suspected for COVID-19 during the epidemic outbreak. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Primary Purpose: Prevention |
||||||||
Condition ICMJE |
|
||||||||
Intervention ICMJE |
|
||||||||
Study Arms ICMJE |
|
||||||||
Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
Recruitment Information | |||||||||
Recruitment Status ICMJE | Not yet recruiting | ||||||||
Estimated Enrollment ICMJE |
524 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | October 30, 2021 | ||||||||
Estimated Primary Completion Date | September 30, 2021 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
|
||||||||
Sex/Gender ICMJE |
|
||||||||
Ages ICMJE | 25 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | Yes | ||||||||
Contacts ICMJE |
|
||||||||
Listed Location Countries ICMJE | Not Provided | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT04446065 | ||||||||
Other Study ID Numbers ICMJE | MEL109042020 | ||||||||
Has Data Monitoring Committee | Yes | ||||||||
U.S. FDA-regulated Product |
|
||||||||
IPD Sharing Statement ICMJE |
|
||||||||
Responsible Party | Elard Koch, PhD, MELISA Institute Genomics & Proteomics Research SpA | ||||||||
Study Sponsor ICMJE | MELISA Institute Genomics & Proteomics Research SpA | ||||||||
Collaborators ICMJE | Universidad Austral | ||||||||
Investigators ICMJE |
|
||||||||
PRS Account | MELISA Institute Genomics & Proteomics Research SpA | ||||||||
Verification Date | September 2020 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |