Tannin Specific Natural Extract for COVID-19 Infection

Study Overview
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Brief Summary
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There is an urgent need to evaluate interventions that could be effective against the infection with SARS-CoV 2. Tannins based wood extracts are an inexpensive and safe product with protective effect in both bacterial and viral infections likely due to its anti- inflammatory, anti-oxidative effects and their modulation of the intestinal microbiota. This randomized controlled trial seeks to evaluate the efficacy of the tannins based dietary supplement ARBOX in positive COVID-19 patients.

Detailed Description
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The epidemic of 2019 novel coronavirus (causing the disease Covid-19) has expanded from Wuhan throughout China and is being exported to a growing number of countries, some of which have seen onward transmission. COVID-19 caused clusters of severe respiratory illness and was associated with 2% mortality. There is currently no vaccine and no specific antiviral treatment recommended for COVID-19. About 20% of the patients were severe and the mainstay of clinical management is largely symptomatic treatment, with organ support in intensive care for seriously ill patients. Therefore, it is urgent to find a safe and effective therapeutic approach to COVID-19. Tannins have been shown to have antioxidant, anti-inflammatory, antimicrobial properties and a regulatory effect on the gastrointestinal metabolism. The investigators will realize a prospective, double-blind, randomized trial to assess the effect of treatment with a dietary supplement (ARBOX), a molecular complex of quebracho and chestnut tannins extract and Vit B12, compared with placebo. 140 COVID-19 patients will be recruited in a single center in Buenos Aires Argentina. 70 patients will receive conventional treatment plus ARBOX (treated group) and 70 patients will receive conventional treatment plus placebo (control group). The effects will be evaluated during the 28 days follow up. The primary end point will be the time of discharge from the hospital. A panel of 27 cytokines level, intestinal microbiota composition and its metabolites will be assessed at day 1 and 14.

Official Title
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Efficacy of Tannin Specific Natural Extract for Coronavirus Disease (COVID-19): Randomized Controlled Trial

Conditions
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COVID-19, SARS-CoV 2, Coronavirus Infection

Intervention / Treatment
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* Dietary Supplement: ARBOX
* Other: PLACEBO


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 18 years of age hospitalized in the general hospitalization room, who meet the definition of Confirmed case COVID-19 (https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion -of-case) Exclusion Criteria: Pregnancy Lactancy Hypersensitivity to polyphenols Patients unable to receive oral medication (severe cognitive impairment, assisted ventilation, impaired state of consciousness) Lack of consent Participation in any other interventional clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: CONTROL<br>Participants will receive placebo supply for 14 days. The placebo will be administrated with the identical dose as described for the test product. Beside patients will receive the standard theraphy, which includes Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy. | Other: PLACEBO<br>* Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for ARBOX<br>|
| Experimental: TREATED<br>Participants will receive a supply of 28 -- 390 mg ARBOX capsules for 14 days. Patients will be supplemented with 2 capsules of ARBOX per day and standard therapy. Standard treatment includes: Antipyretics or Lopinavir / Ritonavir, Azithromycin and Hydroxychloroquine, as appropriate (treatment currently recommended by the department of Infectious Diseases of the Hospital de Clínicas that could undergo to modifications). In addition, if necessary: supplemental O2, non-invasive ventilation, antibiotic therapy. | Dietary Supplement: ARBOX<br>* dry extract of polyphenols (tannins) form quebracho and chestnut 240 mg, B12 vitamin 0.72 µg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to hospital discharge | defined as the time from first dose of polyphenol extract to hospital discharge | Throughout the Study (Day 0 to Day 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day all-cause mortality | proportion | Throughout the Study (Day 0 to Day 28) | 
| invasive ventilation on day 28 | proportion | Throughout the Study (Day 0 to Day 28) | 
| Difference in Pro and antiinflammatory citoquine levels | mean difference | day 1-14 | 
| Difference in fecal intestinal microbiota composition |  | day 1-14 | 
| Negativization of COVID-PCR at day 14 | proportion | day 14 |