Efficacy of Vitamin D Treatment in Mortality Reduction Due to COVID-19.

Efficacy of Treatment With Vitamin D in Patients Diagnosed With COVID-19 Who Presenting Vitamin D Deficiency and Pneumonia.

HYPOTHESIS: The administration of vitamin D supplements to patients who have a positive diagnosis for SARS-Cov-2, acute pneumonia requiring hospital admission and vitamin D deficiency have a more favourable evolution than subjects not treated with vitamin D (placebo). This favourable evolution will translate into a reduction in mortality, fewer ICU admissions and fewer days of stay in hospital.

OBJECTIVES:

PRINCIPAL: To assess whether the group of patients receiving vitamin D supplements have a less severe evolution of their acute pneumonia, translated into lower mortality, than patients who do not receive that supplement.

SECONDARY: 1) To determine the number of intensive care admissions and the number of days of admission in both groups (control group and intervention group). 2) To estimate the prevalence of Vitamin D deficiency in the patients studied and the effectiveness of its supplementation. 3) To establish the degree of complexity of each study group and carry out a cost-effectiveness study.

METHODOLOGY: DESIGN: Clinical trial, randomized, placebo-controlled and double-blind, with two parallel groups The active treatment will be vitamin D (Hydroferol soft capsules of 0.266 mg). The placebo will consist of a tablet with the same external characteristics and with the same treatment scheme but which will not contain any vitamin D active ingredients.

Study Overview

• Status: Completed
• Conditions: SARS Pneumonia; SAR
• Intervention / Treatment: Drug: Vitamin D; Drug: PLACEBO

Detailed Description

HYPOTHESIS: The administration of vitamin D supplements to patients who have a positive diagnosis for SARS-Cov-2, acute pneumonia requiring hospital admission and vitamin D deficiency have a more favourable evolution than subjects not treated with vitamin D (placebo). This favourable evolution will translate into a reduction in mortality, fewer ICU admissions and fewer days of stay in hospital.

OBJECTIVES:

PRINCIPAL: To assess whether the group of patients receiving vitamin D supplements have a less severe evolution of their acute pneumonia, translated into lower mortality, than patients who do not receive that supplement.

SECONDARY: 1) To determine the number of intensive care admissions and the number of days of admission in both groups (control group and intervention group). 2) To estimate the prevalence of Vitamin D deficiency in the patients studied and the effectiveness of its supplementation. 3) To establish the degree of complexity of each study group and carry out a cost-effectiveness study.

METHODOLOGY: DESIGN: Clinical trial, randomized, placebo-controlled and double-blind, with two parallel groups The active treatment will be vitamin D (Hydroferol soft capsules of 0.266 mg). The placebo will consist of a tablet with the same external characteristics and with the same treatment scheme but which will not contain any vitamin D active ingredients.

Inclusion criteria: Adult patients admitted to the Respiratory/Internal Medicine Unit of Santiago hospital of the OSI Araba HUA for acute pneumonia and suffering from a vitamin D deficit (< 30 ng/ml) and a RT-PCR, in nasopharyngeal exudate, positive for SARS-CoV-2.

Exclusion criteria: 1)Patients taking any type of vitamin D supplement. 2)Patients with hypoparathyroidism. 3) Patients in whom the administration of vitamin D is formally contraindicated. 4) Patients who cannot take vitamin D orally.

OUR SIZE: In order to answer to the main objective (mortality reduction 21% versus 50% intervention and control group respectively), we will need a total sample of 108 evaluable subjects-54 patients per group (J Crit Care. 2018;44:300-5).Statistical power 90%,95% statistical significance with possible loss of follow-up of 5% of patients.

A recruitment period of about 12 months is needed.

STATISTICAL ANALYSIS: In order to answer to the main and secondary objectives (mortality and ICU admission), the Chi-square test will be performed and in the event that any of the frequencies is less than 5, the exact Fisher test will be used.

Depending on the distribution of the quantitative variables, the Student t-test for independent samples or the non-parametric Mann-Whitney U-test will be used, respectively.

The analysis criterion will be "by intention to treat". In all cases. The statistical significance will be 95%.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Alava
    • Vitoria-Gasteiz, Alava, Spain, 01002
      • Joaquín Durán Cantolla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Admitted to the Respiratory or Internal medicine Units of Santiago hospital (HUA) due to pneumonia.
• Vitamin D deficiency (25(OH) defined by blood levels below 30 mg/ml.
• Possibility for observation during the treatment period.
• Signing of written consent (oral informed consent exceptionally).
• Positive PCR for diagnosis of sars-cov2 infection

Exclusion Criteria:

• Patients taking any type of vitamin D supplement.
• Patients with hypoparathyroidism.
• Pregnant or lactating women.
• Patients in whom the administration of vitamin D is formally contraindicated (see annex VI).
• Patients who at time of inclusion, cannot take vitamin D orally.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: D VITAMIN GROUP; The administration of vitamin D will be carried out using the following treatment scheme: If vitamin D deficiency (< 30 ng/ml) treatment with 2 capsules of 0.266 mg If vitamin D deficiency (< 40 ng/ml): treatment with 1 capsule of 0.266 mg Blood levels of vitamin D will be determined on day 1, 4, 7 and 14. Based on the results from day 14, a new determination is recommended 4 weeks after starting treatment with the primary care physician who will decide whether to continue or interrupt the treatment. This phase will be carried out outside of the study. In addition, the product should only be administered, if blood calcium and phosphorus levels are within normal limits, as well as if the creatinuria/calciuria ratio is within normal ranges.	Drug: Vitamin D; In case of Vitamin D levels <30 or 40ng/ml patients will take vitamin D supplements.; Other Names: D VITAMIN GROUP
PLACEBO_COMPARATOR: PLACEBO GROUP; The procedure will be the same as in the experimental group but instead of the active component, patients will take placebo capsules exactly the same as above but without the active component.	Drug: PLACEBO; Placebo capsules exactly the same as the above, but without the active component.; Other Names: PLACEO GROUP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MORTALITY	Mortality reduction	At 21 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensive care admissions	Intensive care admissions reduction	At 21 days
Length of hospital stay	Length of hospital stay reduction	AT 21 DAYS
Prevalence of vitamin D deficiency	To assess the prevalence of vitamin D deficiency at baseline	At baseline
Incremental cost effectiveness ratio (ICER)	To calculate the incremental cost per event (mortality) avoided	At 21 days

Collaborators and Investigators

• Sponsor: Bioaraba Health Research Institute
• Collaborators: Fundación Eduardo Anitua
• Investigators: Principal Investigator: Joaquín Durán Cantolla, Bioaraba Health Research Institute

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 9, 2020
• Primary Completion (ACTUAL): November 30, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (ACTUAL): November 9, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2022
• Last Update Submitted That Met QC Criteria: July 14, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Vitamin D; Vitamins
• Other Study ID Numbers: VITD (UAEU)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No