Vitamin D Supplementation in Patients With COVID-19

• ClinicalTrials.gov Identifier: NCT04449718
• Recruitment Status: Completed
• First Posted: June 29, 2020
• Last Update Posted: November 17, 2020
• Sponsor: University of Sao Paulo
• Information provided by (Responsible Party): ROSA MARIA RODRIGUES PEREIRA, University of Sao Paulo

Study Description

Brief Summary:

Coronavirus disease 2019 (COVID-19) was declared an emergency public health problem by the World Health Organization (WHO) in March 2020. Since then, several initiatives by the medical and scientific community have sought alternatives to treat infected individuals, as well as identifying risk or protective factors for the contamination and prognosis of patients. In this perspective, vitamin D supplementation can improve some important outcomes in critically ill patients, being considered a potent immunomodulatory agent. Vitamin D deficiency is a common outcome in critically ill patients, thus making it a modifiable risk factor with great potential for reducing hospital stay and intensive care and mortality. The investigators speculate that vitamin D supplementation could have therapeutic effects in patients with COVID-19.

Condition or disease	Intervention/treatment	Phase
COVID-19	Dietary Supplement: Vitamin D; Dietary Supplement: Placebo	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial
• Actual Study Start Date: June 1, 2020
• Actual Primary Completion Date: October 7, 2020
• Actual Study Completion Date: October 7, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental; Patients will receive 200,000 IU of vitamin D3 on admission + conventional care	Dietary Supplement: Vitamin D; 200,000 IU on admission
Placebo Comparator: Placebo; Patients will receive an equivalent amount of a placebo solution on admission + conventional care	Dietary Supplement: Placebo; 200,000 IU on admission

Outcome Measures

Primary Outcome Measures :

1. Length of hospitalization [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
   total number of days that patient remained hospitalized

Secondary Outcome Measures :

1. Mortality [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
   number of patients that died
2. Number of cases admitted to Intensive Care Unit (ICU) [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
   total number of days that patient remained in ICU
3. Length of use of mechanic ventilator [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
   total number of days that patient remained in mechanic ventilator
4. Number and severity of symptoms [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
5. Inflammatory markers [ Time Frame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month) ]
   C-reactive protein, IL-1alpha (pg/ml), IL-1beta (pg/ml), IL-6 (pg/ml), TNF-alpha (pg/ml), IL-1ra (pg/ml), IL-10 (pg/ml) concentration in the serum
6. C-reactive protein [ Time Frame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month) ]
   serum concentration
7. Vitamin D [ Time Frame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month) ]
   serum concentration
8. Creatinine [ Time Frame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month) ]
   serum concentration
9. Calcium [ Time Frame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month) ]
   serum concentration
10. Physical activity [ Time Frame: Baseline ]
    Baecke questionnaire (higher scores mean a higher physical activity level)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of flu syndrome with hospitalization criteria;
• Respiratory rate ≥ 24irpm and / or saturation <93% in room air, or belonging to the risk group for complications: 1. Chronic diseases: heart disease, diabetes mellitus, systemic arterial hypertension and neoplasms, 2. Immunosuppression, 3. Pulmonary tuberculosis; 4. Obesity;
• Tomographic findings compatible with coronavirus disease.

Exclusion Criteria:

• Patient admitted already under invasive mechanical ventilation;
• Patient admitted with severe acute respiratory syndrome and diagnosed with an etiologic agent other than SARS-CoV-2;
• Prior vitamin D supplementation (above 1000 IU/day);
• Renal failure requiring dialysis or creatinine ≥ 2.0mg/dl;
• Admitted patients with expected hospital discharge in less than 24 hours;
• Patient unable to sign the consent form.

Contacts and Locations

Locations

Brazil

Clinical Hospital of the School of Medicine, University of Sao Paulo

Sao Paulo, Brazil, 05403-000

Sponsors and Collaborators

University of Sao Paulo

Investigators

• Principal Investigator: Rosa Pereira, PhD, MD; School of Medicine, University of Sao Paulo
• Study Director: Bruno Gualano, PhD; School of Medicine, University of Sao Paulo

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fernandes AL, Sales LP, Santos MD, Caparbo VF, Murai IH, Pereira RMR. Persistent or new symptoms 1 year after a single high dose of vitamin D3 in patients with moderate to severe COVID-19. Front Nutr. 2022 Sep 13;9:979667. doi: 10.3389/fnut.2022.979667. eCollection 2022.

Fernandes AL, Murai IH, Reis BZ, Sales LP, Santos MD, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19. Am J Clin Nutr. 2022 Mar 4;115(3):790-798. doi: 10.1093/ajcn/nqab426.

Murai IH, Fernandes AL, Antonangelo L, Gualano B, Pereira RMR. Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19. Clinics (Sao Paulo). 2021 Nov 26;76:e3549. doi: 10.6061/clinics/2021/e3549. eCollection 2021.

Stroehlein JK, Wallqvist J, Iannizzi C, Mikolajewska A, Metzendorf MI, Benstoem C, Meybohm P, Becker M, Skoetz N, Stegemann M, Piechotta V. Vitamin D supplementation for the treatment of COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 May 24;5(5):CD015043. doi: 10.1002/14651858.CD015043.

Murai IH, Fernandes AL, Sales LP, Pinto AJ, Goessler KF, Duran CSC, Silva CBR, Franco AS, Macedo MB, Dalmolin HHH, Baggio J, Balbi GGM, Reis BZ, Antonangelo L, Caparbo VF, Gualano B, Pereira RMR. Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial. JAMA. 2021 Mar 16;325(11):1053-1060. doi: 10.1001/jama.2020.26848.

• Responsible Party: ROSA MARIA RODRIGUES PEREIRA, Dr, University of Sao Paulo
• ClinicalTrials.gov Identifier: NCT04449718
• Other Study ID Numbers: 30959620.4.0000.0068
• First Posted: June 29, 2020
• Last Update Posted: November 17, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by ROSA MARIA RODRIGUES PEREIRA, University of Sao Paulo:

COVID-19; vitamin D; acute respiratory syndrome

Additional relevant MeSH terms:

COVID-19; Vitamin D; Vitamins; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents