Objectives 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. Trial design 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. Participants 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 ). Inclusion Criteria Participants are eligible to be included in the study if the following criteria apply: Any gender ≥18 years old Informed consent for participation in the study Virological diagnosis of SARS-CoV-2 infection (real-time PCR) Exclusion Criteria 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. Main outcomes 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 Randomization 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). Blinding (masking) 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. Trial Status 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. Trial registration ClinicalTrials.gov, number: NCT04403646 , registered on May 27th, 2020. Full protocol 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05281-x.
【저자키워드】 COVID-19, Randomized controlled trial, Inflammation, protocol, Quebracho tannins, Chestnut tannins, gut microbiota, 【초록키워드】 Treatment, Efficacy, SARS-CoV2, clinical trial, therapy, Cytokines, Infectious diseases, Azithromycin, Trial, Hydroxychloroquine, randomization, Clinical symptoms, mechanical ventilation, SARS-COV-2 infection, severity, Lopinavir, Ritonavir, Infection, Ventilation, dietary supplement, Gender, cytokine, Infectious disease, outcome, invasive ventilation, ICU, Randomized, microbiota, Participation, Real-time PCR, Research, Patient, non-invasive ventilation, Alpha, age, Placebo, Consent, Time frame, Informed consent, epidemiological, molecular, recruitment, dissemination, university, disease, patients, platform, placebo-controlled, Inflammatory mediators, administration, intestinal permeability, Blinding, power, dose, closure, Standard therapy, Buenos Aires, fecal, Decline, criteria, double-blind, hypersensitivity, mediators, can not, 24 hours, alpha error, impaired consciousness, assisted ventilation, cognitive, Antibiotic therapy, Definition, Older, number, Enrollment, Sample size, first visit, tannins, control group, Trial registration, supplementary material, status, website, standard treatment, first dose, all-cause mortality, hospital discharge, measure, Registered, eligibility, parallel-group, participant, enrolment, Final, mean difference, supply, treatment allocation, secondary outcome measures, modifications, antipyretics, Department, branch, element, parameter, tannin, All trial participants, computer-generated random numbering, Hospital de Clínicas, Hospital de Clinicas Jose de San Martin, study randomization, Administered, objective, time, secondary, decrease, difference, intestinal, inflammatory mediator, Randomly, enrolled, defined, described, affected, evaluate, blinded, recruited, indicated, addition, Day, screened, undergo, per day, increase in, submitted, assigned, excluded, conditions, Level, Potential, study participant, receive, 1:1, 24 hour, B12, Buenos Aire, diagnosis of SARS-CoV-2, eligible, Hospital de Clínica, lactating, power of 80%, took place, trial participant, 【제목키워드】 Study protocol, COVID-19 patient, natural,