Calcifediol in the Treatment of SARS-CoV-2 Disease (COVID-19). — COVIDIOL  

SARS-CoV 2 Pneumonia Clinical Trial

Official title: Inclusion of Calcifediol in the Hospital Therapeutic Protocol for Treatment of SARS-CoV-2 Disease (COVID-19). Mortality Analysis. Retrospective Study.

Status Recruiting

Clinical Trial Summary

Descriptive, retrospective, observational, anonymous, study to evaluate the potential effect of incorporating calcifediol into the therapeutic protocol of patients hospitalized for COVID-19 on mortality and other outcome variables, such as admission to the Intensive Care Unit (ICU), to "Gerencia de Atención Integrada (GAI) de Albacete". "Complejo Hospitalario Universitario de Albacete". Albacete (Spain)", based on the files of the MXXI medical records, Information System of the Laboratory (ISL) and Pharmacy.

Clinical Trial Description

The coronavirus disease-19 (COVID-19) pandemic, caused by the severe acute respiratory syndrome β-coronavirus (SARS-CoV-2), is one of the greatest challenges facing modern medicine and public health systems worldwide [1]. Since its appearance in December 2019[2], it has caused nearly 7 million deaths, recognized, and confirmed worldwide (https://www.worldometers.info/coronavirus/?), with high acute and post-acute morbidity [3], making it one of the deadliest in human history, with a devastating impact on national economies worldwide [4].

In the first outbreaks of COVID-19, although 80% were asymptomatic or had mild symptoms, 20% of patients developed severe symptoms, and 5% presented acute respiratory distress syndrome (ARDS), septic shock and accompanied multi-organ organ failure. of a high risk of death. Numerous risk factors have been described that influence the poor outcome of these patients, such as age, sex, high blood pressure, chronic obstructive pulmonary disease, diabetes, obesity, chronic lung and digestive diseases, asthma, chronic heart disease and cancer, D-dimer. greater than 1000) or a high SOFA ( Sequential Organ Failure Assessment Score). It has also been observed that patients with no a priori risk factors, may have a poor outcome [5].

The scientific community immediately proposed strong social containment measures, quickly developed effective vaccines to prevent the appearance of severe clinical forms of COVID-19 [6], and new treatments against all aspects of the disease: antiviral agents, anti-inflammatory agents, antithrombotic therapies, to hypoxemic acute respiratory failure, therapies with anti-SARS-CoV-2 antibodies (neutralizing), modulators of the renin-angiotensin-aldosterone system and vitamins [7], so that social and economic activity has gradually recovered worldwide [4].

However, at the current time, there are some indications that hospital admissions for COVID-19 are on the rise again, so the pandemic seems far from over and future waves of infection are likely [8,9].

These indications update and highlight again the repositioning strategy used since the beginning of the pandemic for the use of safe drugs, approved for another indication, and redirected to improve symptoms and clinical outcomes in patients with COVID-19. Various drugs have been investigated with this strategy and many studies have been published, some of them successful [10].

In this sense, in the first months of the pandemic, on the basis of biological plausibility, we thought that the activation of the vitamin D receptor (VDR) signalling pathway of the vitamin D endocrine system (VDES) could produce beneficial effects in COVID 19, [11], by improving innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, mitigating the subsequent reactive hyperinflammatory phase of the host, decreasing the cytokine/chemokine storm, modulating the expression of the renin angiotensin system - (RAAS), and neutrophil activity, maintaining the integrity of the pulmonary/intestinal epithelial barrier, stimulating epithelial repair and directly and indirectly reducing the increase in coagulability and prothrombotic tendency associated with a severe course of COVID- 19 and its complications [12]. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25-hydroxyvitamin D (25(OH)D) status, in patients with SARS-CoV-2 infection may significantly reduce the risk of distress syndrome. acute respiratory syndrome (ARDS) and the development of severe COVID-19 [13].

We decided to use calcifediol, prohormone and cornerstone of the VDES, and substrate for the synthesis of the system's hormone, calcitriol [14]. The poor availability of calcifediol in the general population [15], most marked in patients affected by COVID [16], means that the potential protection that VDR/VDES stimulation confers against various aspects of the disease is lost.

Calcifediol provides pharmacokinetic advantages, which give it a certain functional superiority over native vitamin D3 and even over the hormonal form of VDES, calcitriol, for its use in COVID-19. It is very hydrophilic and, therefore, after oral ingestion, it is absorbed through the portal venous system and does not require hydroxylation at the 25 position, immediately increasing optimal circulating concentrations of 25(OH)D3 [17]. Therefore, even administered orally, it is available at high concentrations within a few hours, and in a stable manner, to be a substrate for calcitriol synthesis in kidney and other target organs in COVID-19 [18].

The clinical trial pilot study and several observational intervention studies using relatively high doses of calcifediol (0.532 µg on day 1 and 0.266 µg on days 3, 7, 14, 21 and 28 decreased the severity of the disease, dramatically reducing the need for ICU admission, severity, and mortality rate [19,20,21] Therefore, using calcifediol at the doses described for rapid correction of 25(OH)D deficiency in all patients in the early stages of COVID-19, in association with the best available therapy, was assessed as a good option. for the treatment of COVID. For this reason, on January 24, 2021, our hospital CALCIFEDIOL was incorporated into the protocol "RECOMMENDATIONS FOR ACTION AND TREATMENT OF THE CORONAVIRUS SARS-CoV-2 DISEASE (COVID-19) version 11.1. ;

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• SARS-CoV 2 Pneumonia

• NCT number: NCT06279910
• Study type: Observational
• Source: Complejo Hospitalario Universitario de Albacete
• Contact: Jose A Blazquez, MD
• Phone: +34967597100
• Email: jblazquez@sescam.jccm.es
• Status: Recruiting
• Start date: February 21, 2024
• Completion date: April 25, 2024