Cholecalciferol to Improve the Outcomes of COVID-19 Patients (CARED)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04411446 |
|
Recruitment Status :
Not yet recruiting
First Posted : June 2, 2020
Last Update Posted : June 4, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 1265 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| COVID | Drug: Vitamin D Drug: Placebo | Phase 4 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1265 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| 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 1065 patients to evaluate the second primary outcome (need for high dose of oxygen supplementation or mechanical ventilation). |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | 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. |
| Primary Purpose: | Treatment |
| Official Title: | Randomized Controlled Trial of High Dose of Vitamin D as Compared With Placebo to Prevent Complications Among COVID-19 Patients |
| Estimated Study Start Date : | June 15, 2020 |
| Estimated Primary Completion Date : | December 15, 2020 |
| Estimated Study Completion Date : | December 28, 2020 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Vitamin D
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
5 capsules of 100.000 UI Vitamin D orally given all at once. One dose.
Other Name: Cholecalciferol |
|
Placebo Comparator: Placebo
5 capsules containing placebo. The intervention will be 5 capsules given in one-time oral intake.
|
Drug: Placebo
5 capsules of containing placebo orally given all at once. One dose. |
- 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 <300.
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.
- Change in oxygen saturation. [ Time Frame: One week ]
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.
- Oxygen desaturation. [ Time Frame: One week ]
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.
- Change in Quick SOFA score. [ Time Frame: 30 days. ]
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.
- Myocardial infarction. [ Time Frame: 30 days ]
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.
- Stroke. [ Time Frame: 30 days ]
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.
- Acute kidney injury. [ Time Frame: 30 days ]
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.
- Pulmonary thromboembolism. [ Time Frame: 30 days ]
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.
- Combined endpoint (stroke, myocardial infarction, acute kidney injury and pulmonary thromboembolism. [ Time Frame: 30 days ]
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.
- Admission to ICU. [ Time Frame: 30 days ]
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.
- Invasive Mechanical Ventilation. [ Time Frame: 30 days ]The start of mechanical ventilation invasive during the hospitalization until 30 days, the death or discharge whichever occur first.
- Hospital Length of Stay. [ Time Frame: 30 days. ]
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.
- ICU length of stay. [ Time Frame: 30 days ]
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.
- Death [ Time Frame: 30 days. ]Death of any cause during the hospitalization until 30 days or discharge whichever occur first.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- SARS-CoV-2 confirmed infection;
- Admission to a hospital in the last 24 hs;
- 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);
- Signed Written consent.
Exclusion Criteria:
- <18 years old;
- Women in childbearing age;
- 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;
- Unavailability to 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04411446
| Contact: Javier Mariani, MD | +541142109000 ext 1523 | ja_mariani@hotmail.com | |
| Contact: Laura Antonietti, MD MSc | +541142109000 ext 3759 | laurayantonietti@gmail.com |
| Argentina | |
| Hospital de Alta Complejidad en Red El Cruce | |
| Florencio Varela, Buenos Aires, Argentina, 1888 | |
| Contact: Sebastián Maristany, MD +541142109000 ext 1528 semaristany@hotmail.com | |
| Study Director: | Walter Manucha, PhD | IMBECU, Univ Nac de Cuyo, Mendoza, Argentina | |
| Principal Investigator: | 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 | Universidad Maimónides | |
| 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 |
| Responsible Party: | Vitamin D Study Group |
| ClinicalTrials.gov Identifier: | NCT04411446 |
| Other Study ID Numbers: |
001 |
| First Posted: | June 2, 2020 Key Record Dates |
| Last Update Posted: | June 4, 2020 |
| Last Verified: | May 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
|
COVID coronavirus SARS-CoV-2 |
Vitamin D Cholecalciferol Respiratory insufficiency |
|
Vitamin D Cholecalciferol Vitamins Micronutrients Nutrients |
Growth Substances Physiological Effects of Drugs Bone Density Conservation Agents Calcium-Regulating Hormones and Agents |