Efficacy of a Dietary Supplementation in Reducing Hospital Admissions for COVID-19. Randomized Clinical Trial (CoVIT)

Efficacy of Micronutrient Dietary Supplementation in Reducing Hospital Admissions for COVID-19: A Double-blind, Placebo-controlled, Randomized Clinical Trial

A double-blind, placebo-controlled, randomized clinical trial to assess efficacy of micronutrient dietary supplementation in reducing hospital admissions for COVID-19 and incidence of Long Covid.

We want to assess the need for hospital admission for severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) infection in outpatients diagnosed of COVID-19 disease, taking a micronutrient supplementation for 14 days. The outcome Will be measured within 1 month after beginning the study treatment. The patients will be followed-up for a period of 180 days for the incidence of Long Covid

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Dietary supplement: Vitamin and trace elements; Dietary supplement: Placebo

Detailed Description

• Type of study/ Design: Randomized, double-blind, placebo-controlled clinical trial.
• Sponsor: Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol / Hospital Universitari Germans Trias i Pujol ( IGTP / HUGTIP)
• Title of the clinical trial: Efficacy of micronutrient dietary supplementation in reducing hospital admissions for COVID-19 and Long Covid: A double-blind, placebo-controlled, randomized clinical trial.
• Protocol code: CoVIT Clinical Trial
• NºClinicaltrials.gov: Pending
• Coordinating researcher: Dra. Teresa-Maria Tomasa-Irriguible.
• Recruiting Center: Germans Trias i Pujol University Hospital (HUGTIP)
• Ethical Committee for clinical Investigation (CEI): Germans Trias i Pujol University Hospital CEI.
• Monitoring: Clinical Research Associate at UPIC (Unitat Polivalent d'Investigació Clínica) Clinical Trial Unit- IGTP
• Study treatments: Dietary supplement with micronutrients and Placebo
• Test phase: Not applicable.
• Main objective: Evaluation of the effectiveness of supplementation with a dietary supplement to improve the need for hospital admission for SARS-CoV-2 infection, and incidence of Long Covid.
• Study pathology: COVID-19.
• Main variable: The need for hospital admission of SARS-CoV-2 documented infection and the incidence of Long Covid
• Study population and total number of patients: Patients of the health system of the Northern Metropolitan Area of Catalan Health Institution with symptoms compatible with SARS-CoV-2 infection. A total of 300 people (150 treated with dietary supplement and 150 with placebo).
• Duration of treatment: 14 days.
• Patients follow-up: 180 days

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Informed Consent Form signed.
2. Patients with symptoms compatible with COVID-19: cough and fever who not fulfil criteria of hospitalization and will be in outpatient care.
3. Positive polymerase chain reaction (PCR) or transcription-mediated amplification (TMA) test or rapid antigen test for severe acute respiratory syndrome Corona Virus-2 (SARS-CoV-2) or diagnostic test available.
4. Age ≥ 18 years
5. Availability to meet the requirements of the protocol.

Exclusion Criteria:

1. Intake of any micronutrient supplement during the month prior to inclusion.
2. Patients fulfilling hospitalization criteria.
3. Previous allergies to the micronutrient components and excipients.
4. Age ≥ 90 years with any comorbidity (diabetes, hypertension, obesity, heart disease, respiratory disease)
5. Participation in other research that requires experimental intervention (does not include observational studies) in the previous month before signing the informed consent form.
6. Detection by the researcher of lack of knowledge or willingness to participate and comply with all the requirements of the protocol.
7. Any other findings that at the discretion of the researcher may compromise protocol performance or significantly influence the interpretation or results of the effects of the nutritional supplement
8. Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Micronutrient dietary supplement effervescent tablet; Tablet containing: Retinol (Vitamin A) 700 mcg; Cholecalciferol (Vitamin D3) 10 mcg; Alpha-Tocopherol (Vitamin E) 45 mg; Ascorbic acid (vitamin C) 1000 mg; Pyridoxine (Vitamin B6) 6.5 mg; Cyanocobalamin (Vitamin B12) 9.6 mg; Folic acid 400 mg; Iron 5 mg; Zinc 10 mg; Selenium 110 mg; Copper 0.9 mg; Excipients	Dietary supplement: Vitamin and trace elements; Dietary supplement oral route, once a day, during 14 days
Placebo Comparator: Placebo dietary supplement effervescent tablet; Effervescent tablet with only the excipients.; Sucralose 13 mg; Sodium Chloride 20 mg; Potassium Acesulfam 22.5 mg; Orange P 55 mg; Sodium Carbonate 70 mg; Betacarotene 100 mg; Malic Acid 800 mg; Citric Acid 960 mg; Sodium bicarbonate 1,000 mg; Isomalt 1,459.50 mg	Dietary supplement: Placebo; Dietary supplement (placebo) oral route, once a day, during 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for hospital admission	The need for hospitalization of documented SARS-CoV-2 infection (positive polymerase chain reaction or transcription-mediated amplification test or antigen test or positive serology or diagnostic test available) over the course of the disease	From baseline to 1 month after beginning the study treatment
Incidence of Long Covid.	Incidence of long Covid or symptoms persistence following World Health Organization definition	6 months after beginning the study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory parameters	Evaluation of C-Reactive Protein, InterLeukin-6 and D-dimer progression during the clinical course of SARS-CoV-2 infection in outpatients	From baseline to 30 days of the study treatment ending
Thromboembolic disease	Evaluation of thromboembolic disease developed during the clinical course of SARS-CoV-2 infection	From baseline to 30 days of the study treatment ending
Oxygen supplementation	Assess the need for oxygen therapy during the clinical course of the infection	From baseline to the study follow-up period: Maximum 3 months
High-Flow oxygen supplementation	The need for high-flow oxygen therapy during the clinical course of infection	From baseline to the study follow-up period: Maximum 3 months
Invasive mechanical ventilation	The cumulative incidence of mechanical ventilation requirement for SARS-CoV-2 infection documented	From baseline to the study follow-up period: Maximum 3 months
Tracheostomy	The need for tracheostomy during the clinical course of SARS-CoV-2 infection	From baseline to the study follow-up period: Maximum 3 months
Renal replacement	The need for renal replacement therapies during the clinical course of SARS-CoV-2 infection	From baseline to the study follow-up period: Maximum 3 months
Death	The cumulative incidence of death from SARS-CoV-2 infection is documented	From baseline to the study follow-up period: Maximum 3 months
Intensive Care Unit Admission	The cumulative incidence of admission to intensive care for SARS-CoV-2 infection documented	From baseline to the study follow-up period: Maximum 3 months
Cumulative hospital admission	The cumulative incidence of hospital admission for a documented SARS-CoV-2 infection	From baseline to the study follow-up period: Maximum 3 months
Hospitalization needs (days)	Number of days hospitalized for a SARS-CoV-2 documented infection	From baseline to the study follow-up period: Maximum 3 months
Survival	Survival	From baseline to the study follow-up period: Maximum 3 months
Adverse events	Adverse events	From baseline to the study follow-up period: Maximum 3 months
Serious Adverse Events	Serious adverse events (hospital admissions and mortality)	From baseline to the study follow-up period: Maximum 3 months
Micronutrient basal status (Vitamin B1, Vitamin B6, 25-OH-Vitamin D and Folic Acid	Evaluation of micronutrient status prior to the nutritional supplement administration (in ng/mL)	Within day 1 at study inclusion
Micronutrient basal status (Vitamin B12)	Evaluation of micronutrient status prior to the nutritional supplement administration in pg/mL	Within day 1 at study inclusion
Micronutrient basal status (Iron, Zinc and Copper )	Evaluation of micronutrient status prior to the nutritional supplement administration in mcg/dL	Within day 1 at study inclusion
Micronutrient basal status (Vitamin A and Vitamin E)	Evaluation of micronutrient status prior to the nutritional supplement administration in mg/L	Within day 1 at study inclusion
Micronutrient basal status (Selenium )	Evaluation of micronutrient status prior to the nutritional supplement administration in mcg/L	Within day 1 at study inclusion
Micronutrient basal status (Vitamin C)	Evaluation of micronutrient status prior to the nutritional supplement administration in mg/dL	Within day 1 at study inclusion
Micronutrient status at hospital admission (Vitamin B1, Vitamin B6, 25-OH-Vitamin D and Folic Acid)	Evaluation of micronutrient status in patients requiring hospitalization in ng/mL	Within the first day of hospital admission
Micronutrient status at hospital admission ( Vitamin B12)	Evaluation of micronutrient status in patients requiring hospitalization in pg/mL	Within the first day of hospital admission
Micronutrient status at hospital admission (Iron, Zinc and Copper)	Evaluation of micronutrient status in patients requiring hospitalization in mcg/dL	Within the first day of hospital admission
Micronutrient status at hospital admission (Vitamin A and Vitamin E)	Evaluation of micronutrient status in patients requiring hospitalization in mg/L	Within the first day of hospital admission
Micronutrient status at hospital admission (Selenium)	Evaluation of micronutrient status in patients requiring hospitalization in mcg/L	Within the first day of hospital admission
Micronutrient status at hospital admission (Vitamin C)	Evaluation of micronutrient status in patients requiring hospitalization in mg/dL	Within the first day of hospital admission
Micronutrient status at end of study (Vitamin B1, Vitamin B6, 25-OH-Vitamin D and Folic Acid)	Evaluation of micronutrient status after the study treatment in ng/mL	Within 90 days of the study treatment ending
Micronutrient status at end of study (Vitamin B12)	Evaluation of micronutrient status after the study treatment in pg/mL	Within 90 days of the study treatment ending
Micronutrient status at end of study (Iron, Zinc, and Copper)	Evaluation of micronutrient status after the study treatment in mcg/dL	Within 90 days of the study treatment ending
Micronutrient status at end of study (Vitamin A and Vitamin E)	Evaluation of micronutrient status after the study treatment in mg/L	Within 90 days of the study treatment ending
Micronutrient status at end of study (Selenium)	Evaluation of micronutrient status after the study treatment in mcg/L	Within 90 days of the study treatment ending
Micronutrient status at end of study (Vitamin C)	Evaluation of micronutrient status after the study treatment in mg/dL	Within 90 days of the study treatment ending
Persistence (or not) of Covid-19 Clinical Symptoms (directly asking patient for peristence of Neurologic, Psicologic, Digestive, Cardiovascular, Respiratory and Osteomuscular Symptoms).	Assess the Post-Covid19 Persistent Symptoms, directly asking patient for Symptoms at the moment of an On site visit at Day 90 and at thelephonic contact on Day 180. Questionnaire to the patient to asess persistent symptoms on the following areas: Neurologic: Montreal Cognitive Assessment (Mo-CA-BLIND) and Persistent cefalea Psicologic: Anxiety, depression, sleep and mood transtorns Digestive: dispepsia, diarrea, constipation Cardiovascular: tachicardia, arrhythmia, acute mycardial infarction and Ictus Respiratory: dispnea, chest pain Osteomuscular: astenia, artralgia and myalgia and other symptoms expressed by the patient.	From baseline to the study follow-up period: Maximum 6 months.
Cognitive status	Assess the Post-Covid19 cognitive status with MoCA-Blind test.	At baseline and at Day 180.
EQ-5D	Assess the evolution of quality of life during the study. EQ-5D-5L quality of life questionnaire will be administered	At baseline and at Day 180.

Collaborators and Investigators

• Sponsor: Fundació Institut Germans Trias i Pujol
• Collaborators: Germans Trias i Pujol Hospital
• Investigators: Principal Investigator: Teresa M Tomasa-Irriguible, MD-PhD, Hospital Germans Trias i Pujol- Intensive Care Unit

Publications and helpful links

General Publications

• Shakoor H, Feehan J, Al Dhaheri AS, Cheikh Ismail L, Ali HI, Alhebshi SH, Apostolopoulos V, Stojanovska L. Role of vitamin D supplementation in aging patients with COVID-19. Maturitas. 2021 Oct;152:63-65. doi: 10.1016/j.maturitas.2021.03.006. Epub 2021 Mar 16. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2021
• Primary Completion (Actual): October 26, 2023
• Study Completion (Actual): October 26, 2023

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Dietary Supplement
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Micronutrients; Trace Elements
• Other Study ID Numbers: CoVIT Clinical Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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