- Open Access
Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial
Trials volume 22, Article number: 310 (2021)
This research aims to study the efficacy of tannins co-supplementation on disease duration, severity and clinical symptoms, microbiota composition and inflammatory mediators in SARS-CoV2 patients.
This is a prospective, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy of the administration of the dietary supplement ARBOX, a molecular blend of quebracho and chestnut tannins extract and Vit B12, in patients affected by COVID-19.
18 years of age or older, admitted to Hospital de Clinicas Jose de San Martin, Buenos Aires University (Argentina), meeting the definition of "COVID-19 confirmed case" (https://www.argentina.gob.ar/salud/coronavirus-COVID-19/definicion-de-caso).
Participants are eligible to be included in the study if the following criteria apply:
≥18 years old
Informed consent for participation in the study
Virological diagnosis of SARS-CoV-2 infection (real-time PCR)
Participants are excluded from the study if any of the following criteria apply:
Pregnant and lactating patients
Patients who cannot take oral therapy (with severe cognitive decline, assisted ventilation, or impaired consciousness)
Hypersensitivity to polyphenols
Patients already in ICU or requiring mechanical ventilation
Patients already enrolled in other clinical trials
Decline of consent
Intervention and comparator
Experimental: TREATED ARM
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.
Placebo Comparator: CONTROL ARM
Participants will receive placebo supply for 14 days. The placebo will be administered with the identical dose as described for the test product.
All trial participants will receive standard therapy, 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.
Primary Outcome Measures:
Time to hospital discharge, defined as the time from first dose of ARBOX to hospital discharge [ Time Frame: Throughout the Study (Day 0 to Day 28) ]
Secondary Outcome Measures:
28-day all-cause mortality [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion
Invasive ventilation on day 28 [ Time Frame: Throughout the Study (Day 0 to Day 28) ]-proportion
Level of inflammation parameters and cytokines [ Time Frame: day 1-14 ] -mean difference
Difference in fecal intestinal microbiota composition and intestinal permeability [ Time Frame: day 1-14 ]
Negativization of COVID-PCR at day 14 [ Time Frame: day 14 ]-proportion
Potential study participants were screened for eligibility 24 hours prior to study randomization. Patients were randomly assigned via computer-generated random numbering (1:1) to receive standard treatment coupled with tannin or standard treatment plus placebo (control group).
Study personnel and participants are blinded to the treatment allocation, as both ARBOX and placebo were packed in identical containers. Thus, all the used capsules had identical appearance.
Numbers to be randomized (sample size)
Considering an alpha error of 5%, a power of 80% a sample size of 70 patients per branch was estimated. 140 patients in total.
The protocol version is number V2, dated May 23, 2020.
The first patient, first visit was on June 12, 2020; the recruitment end date was October 6, 2020.
The protocol was not submitted earlier because the enrollment of some patients took place after the closure of the recruitment on the clinicaltrials platform. In fact, due to the epidemiological conditions, due to the decrease of the cases in Argentina during the summer period, the recruitment stopped t before reaching the number of 140 patients (as indicated in the webpage). However, since there was a new increase in cases, the enrolment was resumed in order to reach the number of patients initially planned in the protocol. The final participant was recruited on February 14, 2021.
ClinicalTrials.gov, number: NCT04403646, registered on May 27th, 2020.
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Availability of data and materials
This work was supported by Indunor/Silvateam SA funding. The company, being the manufacturer, participated by supplying the ARBOX capsules and financed the material and some of the equipment needed to carry out the sampling and the analyses. The funder was not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Ethics approval and consent to participate
This study was approved on 12th June 2020 by the Ethics Committee of the Hospital de Clínicas Jose de San Martin, Buenos Aires University, Argentina. Written informed consent was obtained from all study participants or their legal representatives.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Molino, S., Pisarevsky, A., Mingorance, F.L. et al. Natural tannin extracts supplementation for COVID-19 patients (TanCOVID): a structured summary of a study protocol for a randomized controlled trial. Trials 22, 310 (2021). https://doi.org/10.1186/s13063-021-05281-x
- Randomized controlled trial
- Quebracho tannins
- Chestnut tannins
- gut microbiota