Tannin Specific Natural Extract for COVID-19 Infection (TanCOVID)

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Coronavirus Infection; SARS-CoV 2
• Intervention / Treatment: Dietary supplement: ARBOX; Other: PLACEBO

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1120AAF
    • Hospital de Clínicas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TREATED; 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; dry extract of polyphenols (tannins) form quebracho and chestnut 240 mg, B12 vitamin 0.72 µg
Placebo Comparator: CONTROL; 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; Matching placebo, twice-daily administration BID as described for the test product, identical number of tablets as given for ARBOX

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital de Clinicas José de San Martín
• Collaborators: SILVATEAM
• Investigators: Principal Investigator: Maria M Piskorz, MD, Hospital de Clinicas Universidad de Buenos Aires

Publications and helpful links

General Publications

• Theisen LL, Erdelmeier CA, Spoden GA, Boukhallouk F, Sausy A, Florin L, Muller CP. Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PLoS One. 2014 Jan 31;9(1):e88062. doi: 10.1371/journal.pone.0088062. eCollection 2014.
• Ueda K, Kawabata R, Irie T, Nakai Y, Tohya Y, Sakaguchi T. Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses. PLoS One. 2013;8(1):e55343. doi: 10.1371/journal.pone.0055343. Epub 2013 Jan 25.
• Zhang L, Cheng YX, Liu AL, Wang HD, Wang YL, Du GH. Antioxidant, anti-inflammatory and anti-influenza properties of components from Chaenomeles speciosa. Molecules. 2010 Nov 22;15(11):8507-17. doi: 10.3390/molecules15118507.
• Molino S, Pisarevsky A, Mingorance FL, Vega P, Stefanolo JP, Repetti J, Luduena G, Pepa P, Olmos JI, Fermepin MR, Uehara T, Villapol S, Savidge T, Treangen T, Viciani E, Castagnetti A, Piskorz MM. Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial. Trials. 2021 Apr 28;22(1):310. doi: 10.1186/s13063-021-05281-x.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2020
• Primary Completion (Actual): October 20, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 26, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 19, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections; Infections
• Other Study ID Numbers: HCJSM-20-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No