Covid-19 living Data

Vitamin D vs Standard care/Placebo (RCT)

Hospitalized patients

FOREST PLOTS -2021-10-01

Studies description

Trial *
Publication Elamir YM, Bone (2021) (published paper)
Dates: 2020-09-01 to 2020-12-30
Funding: Not reported/unclear
Conflict of interest: No

Trial NCT04366908
Publication Entrenas Castillo M, J Steroid Biochem Mo (2020) (published paper)

Funding: Public/non profit (Maimónides Biomedical Research Institute of Córdoba)
Conflict of interest: *

Trial NCT04449718
Publication Murai IH, Jama (2021) (published paper)
Dates: 2020-06-02 to 2020-08-27
Funding: Public/non profit (Sao Paulo Research Foundation (FAPESP); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
Conflict of interest: No

Methods
	RCT Blinding: Double blinded, no restrictions
	Location : Multicenter / Brazil Follow-up duration (days): 40
Inclusion criteria	age 18 years or older diagnosis of COVID-19 via PCR testing for SARS-CoV-2 from nasopharyngeal swabs or computed tomography scan findings compatible with the disease (bilateral multifocal ground-glass opacities ≥50%) and diagnosis of flu syndrome with institutional criteria for hospitalization on hospital admission, presenting respiratory rate greater than 24/min, saturation less than 93%while breathing room air, or risk factors for complications (eg, heart disease, diabetes, systemicarterialhypertension,neoplasms, immunosuppression, pulmonary tuberculosis, obesity)followed by COVID-19confirmation.
Exclusion criteria	1) patient unable to read and sign the written informed consent 2) patient already admitted under invasive mechanical ventilation 3) previous vitamin D3 supplementation (> 1000 IU/day) 4) renal failure requiring dialysis or creatinine ≥ 2.0 mg/dL 5) hypercalcemia defined by total calcium > 10.5 mg/dL 6) pregnant or lactating women and 7) patients with expected hospital discharge in less than 24 hours.
Interventions
	Treatment Cholecalciferol 200 000 IU orally dissolved in 10 mL of peanut oil solution once off
	Control Placebo
Participants
	Randomized participants : Cholecalciferol =120 Placebo=120
	Characteristics of participants N= 240 Mean age : NR 133 males Severity : Mild: n=25 / Moderate: n=181 / Severe: n=31 Critical: n=0
Primary outcome
	In the register Length of hospitalization [ Time Frame: From date of randomization until the date of hospital discharge or death, which is usually less than 1 month ]
	In the report Hospital length of stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge.
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published/pre-print article, the trial registry was used in data extraction and assessment of risk of bias. Although the article states that the protocol and statistical analysis plan will be available as supplements, these were not available at time of data extraction. Other than one outcome reported in the registry but not the article (physical activity), there were no substantive differences between the pre-print article and the trial registry in procedures, population, treatments and outcomes. The study was updated on March 25th, 2021 with data from Jama.

Trial NCT04459247
Publication SHADE - Rastogi A, Postgrad Med J (2020) (published paper)

Funding: No specific funding (None)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / USA Follow-up duration (days): 30
Inclusion criteria	Hospitalized patients with COVID-19
Exclusion criteria	Admitted directly to the intensive care unit (ICU) hypercalcemia and/or hyperphosphatemia on admission blood tests untreated disorders of calcium metabolism including hyperparathyroidism, hypoparathyroidism, chronic renal insufficiency with glomerular filtration rate < 30 ml/min prescribed calcitriol for any reason outside of the study.
Interventions
	Treatment Calcitriol 0.5 mcg once a day for 14 days or until discharge, whichever came first
	Control Standard care
Participants
	Randomized participants : Calcitriol=25 Standard care=25
	Characteristics of participants N= 50 Mean age : NR 25 males Severity : Mild: n=24 / Moderate: n=20 / Severe: n=6 Critical: n=0
Primary outcome
	In the register NR
	In the report Outcomes of the effectiveness of calcitriol in the treatment of COVID19 included oxygen requirements, length of hospital stay, need for ICU admission, mortality, and readmission.
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	Only the published article was used in data extraction and assessment of risk of bias. No registry, protocol or statistical analysis plan was available.

Methods
	RCT Blinding: Unblinded
	Location : Single center / Spain Follow-up duration (days): 28
Inclusion criteria	Age ≥ 18 and < 90 years PCR confirmed diagnosis of COVID-19 Radiological image compatible with inflammatory pleuropulmonary exudate Signature of direct or delegated informed consent
Exclusion criteria	Being treated with Calcifediol or Cholecalciferol in any of its presentations and dosages Intolerance or allergy to Calcifediol or its components Pregnancy
Interventions
	Treatment Calcifediol 532 mcg orally on day 1, followed by 266 mcg on days 3 and 7 then weekly until discharge or ICU admission
	Control Standard care
Participants
	Randomized participants : Calcifediol=50 Standard care=26
	Characteristics of participants N= 76 Mean age : NR 45 males Severity : Mild: n=0 / Moderate: n=* / Severe: n=* Critical: n=0
Primary outcome
	In the register Proportion of subjects who enter the ICU; Proportion of subjects who die (Time Frame: At day 28)
	In the report Rate of ICU admission and death
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the published report of the pilot study (journal pre-proof), the study registry was used in data extraction. There is no change from the trial registration in the intervention and control treatments. Pre-specified secondary outcomes included in the registry were not reported. Serum 25OHD concentrations at baseline or during treatment are not available. There were 2 deaths (control arm) out of 80 participants. It was not possible to find the exact timepoint for discharge, though not extracted.

Methods
	RCT Blinding: Double blinded, no restrictions
	Location : Single center / India Follow-up duration (days): 21
Inclusion criteria	1) Individuals with SARS-CoV-2 infection who were mildly symptomatic or asymptomatic with or without co-morbidities (hypertension, diabetes mellitus, chronic obstructive airway disease, chronic liver disease, chronic kidney disease) 2) Patients with vitamin D deficiency defined as 25 (OH)D level<20 ng/ml
Exclusion criteria	1) Patients unable to take oral supplementation like those requiring invasive ventilation or with significant comorbidities like uncontrolled hyperglycaemia or hypertension.
Interventions
	Treatment Cholecalciferol 60 000 IU orally once a day for 7 days, afterwards once a week or once a day for another 7 days (if 25 (OH)D level>50 ng/ml).
	Control Placebo
Participants
	Randomized participants : Cholecalciferol =16 Placebo=24
	Characteristics of participants N= 40 Mean age : NR 20 males Severity : Mild: n=40 / Moderate: n=0 / Severe: n=0 Critical: n=0
Primary outcome
	In the register Virus negativity [ Time Frame: 21 days ]
	In the report Proportions of participants who turn SARS-CoV-2 negative(confirmed twice at 24-hour inter val) before week 3
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	*
General comment	This study is pending contact with authors. In addition to the published article, the trial registry was used in data extraction and assessment of risk of bias. There were some differences between trial registry and published article in terms of population inclusion criteria. There were no differences in terms of study procedures, treatments and outcomes. Patient selection, study procedures and treatments are poorly described in both the published article and trail registry. There is no information about co-interventions given to participants as part of standard care. The study achieved its target sample size.