Clinical trial NCT04411446: Cholecalciferol to Improve the Outcomes of COVID-19 Patients
Official title: Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: COVID
Keywords: COVID
coronavirus
SARS-CoV-2
Vitamin D
Cholecalciferol
Respiratory insufficiency
Lead sponsor: Vitamin D Study Group
Sponsor class: NETWORK
Collaborators: name: Agencia Nacional de Investigación y Desarrollo
First posted: 2020-06-02
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

Detailed description: See above.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* \<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.

Primary outcomes:
measure: Respiratory SOFA.
timeFrame: One week
measure: Need of a high dose of oxygen or mechanical ventilation.
timeFrame: 30 days
Secondary outcomes:
measure: Change in oxygen saturation.
timeFrame: One week
measure: Oxygen desaturation.
timeFrame: One week
measure: Change in Quick SOFA score.
timeFrame: 30 days.
measure: Myocardial infarction.
timeFrame: 30 days
measure: Stroke.
timeFrame: 30 days
measure: Acute kidney injury.
timeFrame: 30 days
measure: Pulmonary thromboembolism.
timeFrame: 30 days
measure: Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.
timeFrame: 30 days
measure: Admission to ICU.
timeFrame: 30 days
measure: Invasive Mechanical Ventilation.
timeFrame: 30 days
measure: Hospital Length of Stay.
timeFrame: 30 days.
measure: ICU length of stay.
timeFrame: 30 days
measure: Death
timeFrame: 30 days.
Other outcomes:
Locations:
city: Florencio Varela
country: Argentina
facility: Hospital de Alta Complejidad en Red El Cruce
state: Buenos Aires
Study officials:
affiliation: IMBECU, Univ Nac de Cuyo, Mendoza, Argentina
name: Walter Manucha, PhD
role: STUDY_DIRECTOR
affiliation: Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche
name: Carlos Tajer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche
name: Laura Antonietti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maimonides University
name: León Ferder, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidad Maimónides - Hospital Universitario Austral
name: Felipe Inserra, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche
name: Javier Mariani, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.