Vitamin A Supplementation in Children With Moderate to Severe COVID-19

Study Overview
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Brief Summary
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Severe acute respiratory syndrome (SARS)-like coronavirus 2 (Sars-CoV-2) pandemia is considered to be the current major global health issue. With no specific treatment or vaccine known to be licensed, empowering the immune system to overcome the inflammatory status associated with the late stages of the disease, particularly by anti-inflammatory nutrients, is of great concern. Effective in reducing both the morbidity and mortality of respiratory infections, including measles, vitamin A and its derivatives are reported to enhance the immune system and/or antibody response to virus vaccinations in children, particularly those with vitamin insufficiency. Retinoids are, therefore, proposed as an adjunct therapy in the treatment of COVID-19. The study is aimed to investigate the effects of vitamin A supplementation on disease improvement in pediatric and adolescent patients with either moderate or severe COVID-19 disease.

Official Title
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The Effect of Vitamin A Supplementation on Disease Improvement of Children With Moderate to Severe COVID-19.

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: Vitamin A supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) aged between 1-month to 18-year old (boy or girl), 2) definitive or clinical diagnosis of severe acute respiratory syndrome (SARS)-like coronavirus 2 (SARS-COV-2) infection (by either a positive SARS-COV-2 polymerase chain reaction (PCR) test or a suggestive computed tomography (CT) scan, 3) no history or evidence of cancer or renal, hepatic, endocrine or viral disorders (including HIV/AIDS), 4) no history of supplementation either with vitamin A (VA) or with a multivitamin containing VA within the last 4 months, and 5) not participated in other clinical trials. Exclusion Criteria: 1) mildly infected with SARS-COV-2 virus, and 2) pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The current phase II, prospective, single-center, single-blinded, randomized placebo-controlled trial, will compare the standard care alone (as the control arm) or in combination with ˝vitamin A supplementation˝ (as the intervention arm) with an allocation ratio of 1:1 in a parallel-group design.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Participants receiving standard treatment alone. | |
| Experimental: Vitamin A<br>Participants receiving standard treatment with an additional vitamin A supplementation. | Dietary Supplement: Vitamin A supplement<br>* The supplementation protocol will be the additional care established by World Health Organization (WHO) and the United Nations International Children ʹs Fund (UNICEF) for measles (1998)(i.e. of 200,000 IU, or 50,000-100,000 IU for children > 1 or for infants of < 1 year of age, respectively).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-day mortality rate | COVID-19 mortality rate is defined as the number of deaths per 100 pediatric COVID-19 cases 28 days from the date of the intervention. | within 28 days from end of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| length of hospital stay | The length of hospital stay is defined as the difference between date of admission and date of discharge of the patient. | on the day of hospital discharge | 
| length of pediatric intensive care unit (PICU) stay | The length of PICU stay is defined as the difference between date of PICU admission and date of PICU discharge of the patient. | on the day of PICU discharge | 
| length of intubation | The length of intubation is defined as the difference between date of beginning and end of intubation | on the day of extubation | 
| length of mechanical ventilation | The length of mechanical ventilation is defined as the difference between date of beginning and end of mechanical ventilation. | the weaning time of mechanical ventilation | 
| multiple organ involvement | Multiple organ involvement is defined as one of either hematological, gastrointestinal, neurological, cardiovascular or hepatorenal complications. | on the day of the particular organ involvement | 
| complete blood count (CBC)/diff | Complete blood count with differential | before and within 3 days from end of intervention | 
| Prothrombin time (PT) | Prothrombin time | before and within 3 days from end of intervention | 
| Partial thromboplastin time (PTT) | Partial thromboplastin time | before and within 3 days from end of intervention | 
| International normalised ratio (INR) | International normalised ratio | before and within 3 days from end of intervention | 
| fibrinogen | fibrinogen | before and within 3 days from end of intervention | 
| troponin | troponin | before and within 3 days from end of intervention | 
| Aspartate transaminase (AST) | Aspartate transaminase | before and within 3 days from end of intervention | 
| Alanine transaminase (ALT) | Alanine transaminase | before and within 3 days from end of intervention | 
| Blood urea nitrogen (BUN) | Blood urea nitrogen | before and within 3 days from end of intervention | 
| Cr | Creatinine | before and within 3 days from end of intervention | 
| Erythrocyte sedimentation rate (ESR) | Erythrocyte sedimentation rate | before and within 3 days from end of intervention | 
| C-reactive protein (CRP) | C-reactive protein | before and within 3 days from end of intervention | 
| Lactate dehydrogenase (LDH) | Lactate dehydrogenase | before and within 3 days from end of intervention | 
| D-dimer | D-dimer | before and within 3 days from end of intervention | 
| ferritin | ferritin | before and within 3 days from end of intervention | 
| procalcitonin | procalcitonin | before and within 3 days from end of intervention | 
| vitamin A concentration | vitamin A concentration | before and within 3 days from end of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin A, inflammation, pediatrics