Cholecalciferol to Improve the Outcomes of COVID-19 Patients

NCT04411446 | Completed Phase 4

• 1 other identifier: 001
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 1

Brief Summary

The recent inception of the coronavirus SARS-CoV-2, responsible for the coronavirus disease (COVID-19), has caused thousands of deaths globally. The most frequently reported complications among COVID-19 patients are from respiratory involvement. Vitamin D has immunomodulatory effects that could protect against COVID-19 infection. Indeed, there is good evidence from randomized clinical trials suggesting that high doses of vitamin D administered during cold seasons prevent viral respiratory infections in at risk individual, and more recently, observational studies suggested that the mortality rate from COVID-19 is inversely correlated with levels of serum 25(OH)vitamin D. The hypothesis of the study is that a high dose of vitamin D given orally to patients admitted to the hospital for COVID-19 will prevent the occurrence of respiratory deragement and other adverse clinical events. To evaluate the aforementioned hypothesis, a randomized, controlled, double-blind, clinical trial comparing a 500.000 UI dose of vitamin D versus placebo among COVID-19 patients at moderate risk, requiring hospitalization but without requirements of critical care at admission was designed. The intervention will be one dose of 500.000 UI given orally or matching placebo. The trial has a sequential design with two steps:

• The first step, projected to include 200 patients, will assess the effects of the intervention on the respiratory SOFA; and
• If there is a detectable effects, the second step, projected to include 1264 patients, will assess the effects on a combined event that includes need of high dose of oxygen or mechanical ventilation. All study outcomes will be measured during the index hospitalization.

Conditions

COVID

Keywords

COVID; coronavirus; SARS-CoV-2; Vitamin D; Cholecalciferol; Respiratory insufficiency

Outcome Measures

Primary Outcomes (2)

• Respiratory SOFA.

  Is the respiratory component of the sequential organ failure assessment score (SOFA score). It is a 4 points scale, each point indicate a deeper respiratory impairment. The score is based on the relationship between the arterial pressure of oxygen (PaO2) and inspired fraction of oxygen (FiO2), as the ratio of both (PaFi). In the cases were arterial blood gas are not measured, the pulse oximetry will be used instead. The respiratory SOFA is as follows: * 1: PaO2/FiO2 \>=300; * 2: PaO2/FiO2 \>=200 and \<300; * 3: PaO2/FiO2 \>=100 and \<200; * 4: PaO2/FiO2 \<100. The minimum respiratory SOFA score will be record on daily basis during first week or to death or discharge, whichever occur first. This outcome is the primary outcome of the first study phase.

  One week

• Need of a high dose of oxygen or mechanical ventilation.

  The start of oxygen supplementation at FiO2 \>40% or the initiation of invasive through orotracheal intubation) or non-invasive ventilation (Continuous positive airway pressure or Bilevel positive airway ventilation). This outcome will be recorded during hospitalization to 30 days, the death or discharge, whichever occur first. This is the primary outcome of the second study phase.

  30 days

Secondary Outcomes (13)

• Change in oxygen saturation.

  One week

• Oxygen desaturation.

  One week

• Change in Quick SOFA score.

  30 days.

• Myocardial infarction.

  30 days

• Stroke.

  30 days

Study Arms (2)

Vitamin D

EXPERIMENTAL

5 capsules containing 100.000 UI of vitamin D each. The intervention will be 5 capsules given in one-time oral intake.

Drug: Vitamin D

Placebo

PLACEBO COMPARATOR

5 capsules containing placebo. The intervention will be 5 capsules given in one-time oral intake.

Drug: Placebo

Interventions

Vitamin D DRUG

5 capsules of 100.000 UI Vitamin D orally given all at once. One dose.

Also known as: Cholecalciferol

Vitamin D

Placebo DRUG

5 capsules of containing placebo orally given all at once. One dose.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• SARS-CoV-2 confirmed infection;
• Admission to a hospital;
• Expected hospitalization in the center for at least for 24 hs;
• Oxygen Saturation \>90% breathing without oxygen supplement;
• Age at least 45 years or the presence of one of the followings risk factors:
• Hypertension;
• Diabetes (type I o II);
• At least moderate COPD or Asthma;
• Cardiovascular disease (history of myocardial infarction, coronary angioplasty, coronary artery bypass grafting or valve replacement surgery);
• Body Mass Index \>=30;
• Signed Written consent.

You may not qualify if:

• \<18 years old;
• Women in childbearing age;
• \>= 72 hs since current admission;
• Requirement for high dose of oxygen (\>5 liters/minute) or mechanical ventilation (non-invasive or invasive);
• History of Chronic kidney disease requiring hemodialysis or chronic liver failure;
• Inability for oral intake;
• Previous treatment with pharmacological vitamin D;
• History of:
• previous treatment with anticonvulsants;
• sarcoidosis;
• malabsorption syndrome;
• Known hypercalcemia.
• Life expectancy less than 6 months;
• Known allergy to the study medication;
• Any condition impeding to bring informed consent.

Sponsors & Collaborators

• Vitamin D Study Group: lead
• Agencia Nacional de Investigación y Desarrollo: collaborator

Study Sites (1)

Hospital de Alta Complejidad en Red El Cruce

San Juan Bautista, Buenos Aires, 1888, Argentina

Location

Related Publications (3)

• Martin Gimenez VM, Inserra F, Tajer CD, Mariani J, Ferder L, Reiter RJ, Manucha W. Lungs as target of COVID-19 infection: Protective common molecular mechanisms of vitamin D and melatonin as a new potential synergistic treatment. Life Sci. 2020 Aug 1;254:117808. doi: 10.1016/j.lfs.2020.117808. Epub 2020 May 15.

  PMID: 32422305 RESULT

• Mariani J, Antonietti L, Tajer C, Ferder L, Inserra F, Sanchez Cunto M, Brosio D, Ross F, Zylberman M, Lopez DE, Luna Hisano C, Maristany Batisda S, Pace G, Salvatore A, Hogrefe JF, Turela M, Gaido A, Rodera B, Banega E, Iglesias ME, Rzepeski M, Gomez Portillo JM, Bertelli M, Vilela A, Heffner L, Annetta VL, Moracho L, Carmona M, Melito G, Martinez MJ, Luna G, Vensentini N, Manucha W. High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial. PLoS One. 2022 May 27;17(5):e0267918. doi: 10.1371/journal.pone.0267918. eCollection 2022.

  PMID: 35622854 DERIVED

• Mariani J, Tajer C, Antonietti L, Inserra F, Ferder L, Manucha W. High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial (CARED-TRIAL). Trials. 2021 Feb 1;22(1):111. doi: 10.1186/s13063-021-05073-3.

  PMID: 33522946 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; Respiratory Insufficiency

Interventions

Vitamin D; Cholecalciferol

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiration Disorders; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids

Study Officials

• Walter Manucha, PhD

  IMBECU, Univ Nac de Cuyo, Mendoza, Argentina

  STUDY DIRECTOR

• Carlos Tajer, MD

  Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche

  PRINCIPAL INVESTIGATOR

• Laura Antonietti, MD

  Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche

  PRINCIPAL INVESTIGATOR

• León Ferder, MD

  Maimonides University

  PRINCIPAL INVESTIGATOR

• Felipe Inserra, MD

  Universidad Maimónides - Hospital Universitario Austral

  PRINCIPAL INVESTIGATOR

• Javier Mariani, MD

  Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will use a placebo identical to the active medication. The members of research team assessing the outcomes will not be aware of the treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Two parallel arms randomized controlled trial. A sequential design will be used with the first primary outcome being the primary outcome for the first step. This step will include 200 patients. After reach this point, a review of the primary outcome (change in respiratory SOFA) will be done. According to these results, the Executive committee will decide to proceed the second step of the study and include the remaining 1064 patients to evaluate the second primary outcome (need for high dose of oxygen supplementation or mechanical ventilation).

Study Record Dates

• First Submitted: May 26, 2020
• First Posted: June 2, 2020
• Study Start: August 11, 2020
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: July 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

AR (1)