COVIDPhase 4CAREDNCT04411446

Cholecalciferol to Improve the Outcomes of COVID-19 Patients

A Phase 4 study testing Vitamin D in people with COVID, run by Vitamin D Study Group at 1 site in Argentina.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: COVID
What is being tested?: Vitamin D
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 218 participants
Where: 1 siteArgentina
Study dates: 11 Aug 2020to 28 Jul 2021
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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;

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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.

Who cannot join

<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;

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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.

Trial locations and contacts

1 site in 1 country.

Argentina1 site

Hospital de Alta Complejidad en Red El Cruce
San Juan Bautista, Buenos Aires, 1888

Other trials in Argentina

About this study

Official title: Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients

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.

Read the detailed description

See above.

Conditions: COVID
Being tested: Vitamin D, Placebo
Keywords: COVID, coronavirus, SARS-CoV-2, Vitamin D, Cholecalciferol, Respiratory insufficiency
Medical subject headings: Coronavirus Infections, Respiratory Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vitamin DDrug
Also called Cholecalciferol
5 capsules of 100.000 UI Vitamin D orally given all at once. One dose.
PlaceboDrug
5 capsules of containing placebo orally given all at once. One dose.

Study groups in NCT04411446
Study group	Role	What they receive
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. Receives: Drug: Vitamin D
Placebo	Placebo comparator	5 capsules containing placebo. The intervention will be 5 capsules given in one-time oral intake. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 30 days

Secondary outcomes (13)

Change in oxygen saturation.
Difference between the oxygen saturation at study entry and the lowest oxygen saturation measured during the first week, the death or discharge, whichever occur first.
The oxygen saturation will be measured by pulse oximetry using commercially available devices.
Measured: One week
Oxygen desaturation.
Oxygen saturation equal or less than 90% in any moment during the hospitalization. This outcome will be measured by pulse oximetry using commercially available devices.
The outcome will be measured during the first week, the death or hospital discharge, whichever occur first.
Measured: One week
Change in Quick SOFA score.
The difference between the Quick SOFA score at study entry and the highest value recorded during the hospitalization.
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days.
Myocardial infarction.
Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition.
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Stroke.
Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician.
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Acute kidney injury.
Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization).
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Pulmonary thromboembolism.
Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography.
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.
Combined outcome of the aforementioned events, Stroke is defined as a focal neurological loss lasting >24 hs as reported by treating physician.
Myocardial infarction is defined as suspicious symptoms with new Q waves in the EKG and enzymatic elevations compatible with the Fourth MI Definition.
Pulmonary thromboembolism is defined as the presence of suspicious symptoms (i.e. dyspnea) confirmed with objective evidence of a thrombus in the pulmonary tree by CT or MRI or Pulmonary Angiography.
Acute kidney injury is defined as an increase of at least 50% in serum creatinine levels (as compared with any previous value during the hospitalization).
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Admission to ICU.
Admission to Intensive Care Unit due to clinical deterioration as judged by the treating physician.
The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Invasive Mechanical Ventilation.
The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.
Measured: 30 days
Hospital Length of Stay.
Total duration of initial hospital stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
In the cases with hospital stays longer than 30 days, it will considered as 30 days.
Measured: 30 days.
ICU length of stay.
Total duration of initial ICU stay in days. The outcome will be measured during the hospitalization until 30 days, the death or discharge whichever occur first.
In the cases with ICU stays longer than 30 days, it will considered as 30 days.
Measured: 30 days
Death
Death of any cause during the hospitalization until 30 days or discharge whichever occur first.
Measured: 30 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Aug 202028 Jul 2021

First posted2 Jun 2020
Study start11 Aug 2020
Primary completion28 Jul 2021
Study completion28 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for COVIDStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
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).
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 218 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04411446
Sponsor's protocol ID: 001
Acronym: CARED
Status last verified: Mar 2021
First submitted: 26 May 2020
Last updated: 30 Jul 2021
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 32422305
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.
PubMed 35622854
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.
PubMed 33522946

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients
ClinicalTrials.gov ID: NCT04411446
Acronym / sponsor ID: CARED / 001
Conditions: COVID
Keywords: COVID, coronavirus, SARS-CoV-2, Vitamin D, Cholecalciferol, Respiratory insufficiency
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 218 participants (actual)
Lead sponsor: Vitamin D Study GroupResearch network
Collaborators: Agencia Nacional de Investigación y Desarrollo
Study start: 11 Aug 2020 (actual)
Primary completion: 28 Jul 2021 (actual)
Study completion: 28 Jul 2021 (actual)
First posted: 2 Jun 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
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).

Arm	Type	Receives
Vitamin D	Experimental	Drug: Vitamin D5 capsules containing 100.000 UI of vitamin D each. The intervention will be 5 capsules given in one-time oral intake.
Placebo	Placebo comparator	Drug: Placebo5 capsules containing placebo. The intervention will be 5 capsules given in one-time oral intake.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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:

Key exclusion criteria (15 listed)

<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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Vitamin DAlso: Cholecalciferol5 capsules of 100.000 UI Vitamin D orally given all at once. One dose.	Drug	Vitamin D
Placebo5 capsules of containing placebo orally given all at once. One dose.	Drug	Placebo

Primary outcome

Respiratory SOFA.
Time frame: One week
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.
Need of a high dose of oxygen or mechanical ventilation.
Time frame: 30 days
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.

13 secondary outcomes

Change in oxygen saturation.
Time frame: One week
Oxygen desaturation.
Time frame: One week
Change in Quick SOFA score.
Time frame: 30 days.
Myocardial infarction.
Time frame: 30 days
Stroke.
Time frame: 30 days
Acute kidney injury.
Time frame: 30 days
Pulmonary thromboembolism.
Time frame: 30 days
Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism.
Time frame: 30 days
Admission to ICU.
Time frame: 30 days
Invasive Mechanical Ventilation.
Time frame: 30 days
Hospital Length of Stay.
Time frame: 30 days.
ICU length of stay.
Time frame: 30 days
Death
Time frame: 30 days.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2021.
Results publication: PubMed 32422305Martin 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.
Derived from this study: PubMed 35622854Mariani 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.
Derived from this study: PubMed 33522946Mariani 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Walter Manucha, PhD study director

IMBECU, Univ Nac de Cuyo, Mendoza, Argentina

Carlos Tajer, MD principal investigator

Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche

Laura Antonietti, MD principal investigator

Hospital de Alta Complejidad El Cruce - Universidad Nacional Arturo Jauretche

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vitamin D in people with COVID, run by Vitamin D Study Group at 1 site in Argentina.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Respiratory SOFA. (time frame: One week). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04411446, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2021.