Calcifediol in the Treatment of COVID 19

April 27, 2023 updated by: Maimónides Biomedical Research Institute of Córdoba

Calcifediol in the Treatment of COVID 19. Modification of Therapeutic Response by Best Available Treatment or Other Treatment or Clinical Variables

Patients hospitalized with COVID-19 treated with calcifediol during the first outbreaks of the pandemic (until the first vaccinations) are compared with the aim of determining the therapeutic, clinical, functional, and biochemical variables that modify the response (admission to ICU or death) to calcifediol during hospitalization for COVID 19

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The ongoing pandemic of coronavirus disease-19 (COVID-19), caused by the β-coronavirus SARS-CoV-2, is the greatest challenge ever faced by modern medicine and public health systems worldwide. In early outbreaks, approximately 20% progressed to severe symptomatology, of which 5% developed acute respiratory distress syndrome (ARDS), septic shock and multi-organ failure accompanied by a high risk of death. In this scenario, the scientific community employed strong social containment measures and developed vaccines effective in preventing severe clinical forms of COVID-19. Vaccines against the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have shown a preventive effect against the occurrence and severity of COVID-19, and social and economic activities are gradually recovering worldwide.

The rapid mutation rate of this virus family including multiple mutations in the receptor binding domain of the spike protein that have been associated with increased transmissibility and immune evasion after natural infection and vaccination, calls into question both the efficacy of vaccines and their long-term safety and the efficacy of monoclonal antibodies withdrawn for lack of effectiveness. Moreover, the cost/benefit of newly licensed oral antivirals for high-risk patients in higher-income countries remains inadequately documented.

These data update the repositioning strategy employed since the beginning of the pandemic for the use of safe drugs, approved for another indication and reproposed to improve symptoms and clinical outcomes in COVID-19 patients.

Numerous drugs have been investigated with this strategy and many studies have been published. Calcifediol (25OH vitamin D3) is one of them. Calcifediol is the prohormone of the vitamin D endocrine system (VDES). It requires hydroxylation to convert to calcitriol (1,25(OH)2 vitamin D3) , the active form that exerts its functions by activating the vitamin D receptor (VDR), which is expressed in the immune system and many other affected organs in COVID, including the lungs.

Available data strongly suggest that treatment with calcifediol can decrease the severity of COVID-19, decreasing the need for intensive care unit (ICU) admissions and decreasing the risk of mortality. It is a cost-effective treatment, without major adverse effects, and widely available, which could have positive implications for the treatment of the disease worldwide.

Another family of repositioned drugs has been the corticosteroids. Commonly used for decades for their immunosuppressive/anti-inflammatory properties by inhibiting the expression of multiple pro-inflammatory cytokines and chemokines, and the (in)activation of various immune cells. However, at the start of the pandemic in 2020, corticosteroid treatment in COVID-19 was formally contraindicated or not recommended.

Corticosteroids had been widely used during outbreaks of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, but review of their use in those epidemics suggested that corticosteroid use could increase mortality and secondary infection rates by delaying viral clearance. Therefore, World Health Organization (WHO) interim guidance on the clinical management of severe acute respiratory infection when SARS-CoV-2 infection was suspected (published on 28 January 2020) advised against the use of corticosteroids unless otherwise indicated.

For this reason, the three studies described that treated COVID with high-dose calcifediol and best available therapy did not use corticosteroids (except rarely and after a consensus clinical decision by the treating physicians). Thus, the results obtained did not have the confounding factor of modulation of innate and acquired immunity by corticosteroid treatment.

Following the RECOVERY trial, one of the largest randomized controlled trials for COVID-19 treatment, clinical practice guidelines were modified worldwide to authorize the standard use of dexamethasone or other corticosteroids as the best available treatment in hospitalized patients with severe COVID-19 requiring intensive oxygen therapy. However, the appropriate time interval for corticosteroid administration is a matter of debate, and the response to treatment is also likely to be related to the natural history of each patient's clinical and biological evolution. In addition, it is unclear how long treatment should last; since prolonged corticosteroid treatment may not be safe, due to interference with clotting and metabolic pathways, disease symptoms and long-term persistence of COVID-19.

Therefore, systemic glucocorticoids, included as the best available treatment, could, depending on the timing of their introduction, modify and/or confound the beneficial effect of calcifediol evidenced in the pre-corticoid stage of the pandemic. Other variables may also act as a confounding factor in the response to calcifediol treatment.

Study Type

Observational

Enrollment (Actual)

728

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Córdoba
      • Cordoba, Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Patients requiring hospital admission due to respiratory infection confirmed by SARS-CoV-2 (radiographic pattern of viral pneumonia and positive PCR for SARS-CoV-2) with a CURB65 severity scale (recommending hospital admission in case of a total score > 1).

Patients meeting ALL inclusion criteria and NO exclusion criteria will be included in the study.

Description

Inclusion Criteria:

  • Age ≥ 18 and < 90 years.
  • Diagnosis confirmed by positive polymerase chain reaction (PCR) for COVID-19.
  • Radiological image compatible with pulmonary involvement by COVID-19.
  • Admission to "Reina Sofia university Hospital (HURS)" Pneumology Department.

Exclusion Criteria:

  • Patients for whom electronic medical record data cannot be collected.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Calcifediol
Drug: Calcifediol
Subjects hospitalized with COVID-19 treated with calcifediol
Best therapy available
Drug: Best available therapy
Subjects hospitalized with COVID-19 treated with Azithromycin, hydroxychloroquine, corticoids and others authorized treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Need for ICU admission
Time Frame: from hospitalization till discharge /death
Measure the need for ICU admission by differentiating the groups calcifediol yes/no; corticosteroids yes/no.
from hospitalization till discharge /death
Mortality
Time Frame: from hospitalization till discharge /death
Measure mortality by differentiating groups: calcifediol yes/no; corticosteroids yes/no.
from hospitalization till discharge /death
Composite variable poor prognosis, (ICU&death)
Time Frame: from hospitalization till discharge /death
Measure the composite variable poor prognosis, (ICU&death) by differentiating the groups calcifediol yes/no; corticosteroids yes/no.
from hospitalization till discharge /death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
clinical variables that calcifediol response
Time Frame: from hospitalization till discharge /death
To detect clinical variables that may modify the response to calcifediol.
from hospitalization till discharge /death
drug modifying calcifediol response
Time Frame: from hospitalization till discharge /death
To detect clinical variables that may modify the response to calcifediol.
from hospitalization till discharge /death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maimónides Biomedical Research Institute of Córdoba

Investigators

  • Principal Investigator: Luis M Entrenas Costa, MD, Hospital Universitario Reina Sofia de Cordoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2022

Primary Completion (Actual)

April 17, 2023

Study Completion (Actual)

April 17, 2023

Study Registration Dates

First Submitted

April 17, 2023

First Submitted That Met QC Criteria

April 17, 2023

First Posted (Actual)

April 19, 2023

Study Record Updates

Last Update Posted (Actual)

April 28, 2023

Last Update Submitted That Met QC Criteria

April 27, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TD-CCRC-21

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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