Clinical trial NCT04449718: Vitamin D Supplementation in Patients With COVID-19
Official title: Vitamin D Supplementation in Patients With COVID-19: A Randomized, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19
Keywords: COVID-19
vitamin D
acute respiratory syndrome
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
First posted: 2020-06-29
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Length of hospitalization
timeFrame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
Secondary outcomes:
measure: Mortality
timeFrame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
measure: Number of cases admitted to Intensive Care Unit (ICU)
timeFrame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
measure: Length of use of mechanic ventilator
timeFrame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
measure: Number and severity of symptoms
timeFrame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month
measure: Inflammatory markers
timeFrame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)
measure: C-reactive protein
timeFrame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)
measure: Vitamin D
timeFrame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)
measure: Creatinine
timeFrame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)
measure: Calcium
timeFrame: Baseline, 14 days after hospitalization and at the moment of hospital discharge or death (usually less than 1 month)
measure: Physical activity
timeFrame: Baseline
Other outcomes:
Locations:
city: Sao Paulo
country: Brazil
facility: Clinical Hospital of the School of Medicine, University of Sao Paulo
Study officials:
affiliation: School of Medicine, University of Sao Paulo
name: Rosa Pereira, PhD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: School of Medicine, University of Sao Paulo
name: Bruno Gualano, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.