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

Study Overview
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Brief Summary
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A double-blind, placebo-controlled, randomized clinical trial to assess efficacy of micronutrient dietary supplementation in reducing hospital admissions for COVID-19. 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.

Detailed Description
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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: 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. Study pathology: COVID-19. Main variable: The need for hospital admission of SARS-CoV-2 documented infection 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

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

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: Vitamin and trace elements
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent Form signed. Patients with symptoms compatible with COVID-19: cough and fever who not fulfil criteria of hospitalization and will be in outpatient care. 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. Age ≥ 18 years Availability to meet the requirements of the protocol. Exclusion Criteria: Intake of any micronutrient supplement during the month prior to inclusion. Patients fulfilling hospitalization criteria. Previous allergies to the micronutrient components and excipients. Age ≥ 90 years with any comorbidity (diabetes, hypertension, obesity, heart disease, respiratory disease) Participation in other research that requires experimental intervention (does not include observational studies) in the previous month before signing the informed consent form. Detection by the researcher of lack of knowledge or willingness to participate and comply with all the requirements of the protocol. 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 Pregnancy or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A double-blind, placebo-controlled, randomized clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Micronutrient dietary supplement effervescent tablet<br>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<br>* Dietary supplement oral route, once a day, during 14 days<br>|
| Placebo Comparator: Placebo dietary supplement effervescent tablet<br>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<br>* Dietary supplement (placebo) oral route, once a day, during 14 days<br>|

What is the study measuring?
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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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary Supplement