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

• ClinicalTrials.gov Identifier: NCT04403646
• Recruitment Status: Terminated
• First Posted: May 27, 2020
• Last Update Posted: December 22, 2020
• Sponsor: Hospital de Clinicas José de San Martín
• Collaborator: SILVATEAM
• Information provided by (Responsible Party): Maria Marta Piskorz, Hospital de Clinicas José de San Martín

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19; SARS-CoV 2; Coronavirus Infection	Dietary Supplement: ARBOX; Other: PLACEBO	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy of Tannin Specific Natural Extract for Coronavirus Disease (COVID-19): Randomized Controlled Trial
• Actual Study Start Date: June 12, 2020
• Actual Primary Completion Date: October 20, 2020
• Actual Study Completion Date: November 1, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Time to hospital discharge [ Time Frame: Throughout the Study (Day 0 to Day 28) ]
   defined as the time from first dose of polyphenol extract to hospital discharge

Secondary Outcome Measures :

1. 28-day all-cause mortality [ Time Frame: Throughout the Study (Day 0 to Day 28) ]
   proportion
2. invasive ventilation on day 28 [ Time Frame: Throughout the Study (Day 0 to Day 28) ]
   proportion
3. Difference in Pro and antiinflammatory citoquine levels [ Time Frame: day 1-14 ]
   mean difference
4. Difference in fecal intestinal microbiota composition [ Time Frame: day 1-14 ]
5. Negativization of COVID-PCR at day 14 [ Time Frame: day 14 ]
   proportion

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Argentina

Hospital de Clinicas

Buenos Aires, Argentina, C1120AAF

Sponsors and Collaborators

Hospital de Clinicas José de San Martín

SILVATEAM

Investigators

• Principal Investigator: Maria M Piskorz, MD; Hospital de Clinicas Universidad de Buenos Aires

More Information

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.

• Responsible Party: Maria Marta Piskorz, Neurogastroenterologist at Hospital de Clinicas, Principal Investigator, Hospital de Clinicas José de San Martín
• ClinicalTrials.gov Identifier: NCT04403646
• Other Study ID Numbers: HCJSM-20-005
• First Posted: May 27, 2020
• Last Update Posted: December 22, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infection; Coronavirus Infections; Severe Acute Respiratory Syndrome; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases