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Single center, open label randomized clinical trial.
Study location: tertiary hospital center (University Hospital Split, Croatia). All COVID-19 patients with positive PCR test admitted to ICU and in need for respiratory support will be eligible for inclusion in this study.
Patients admitted to ICU with severe COVID-19 disease and in need for invasive or non-invasive respiratory support with low levels of vitamin D (<50 nmol/l) measured on admission. All patients are older than 18 years and have confirmed COVID-19 disease with PCR test.
Intervention:
All patients included in this study will receive standard of care. Patients randomized into intervention group will be receiving 10 000 IU of cholecalciferol daily. Supplement will be administered orally or via gastric tube during ICU stay or for at least 14 days in case of ICU discharge before day 14. Supplementation will begin within 48 hours of admission to ICU. Supplement will be prepared and administered by experienced nursing staff. For patients receiving supplementation, vitamin D levels will be checked on days 7 and 14. In case that vitamin D levels are > 150 nmol/l or if the calcium levels are consistently > 2.6 mmol/l, further supplementation will be stopped.
Outcomes:
Primary outcome is number of days spent on ventilator.
Secondary outcomes: all-cause mortality on day 28, all-cause mortality on day 60, mortality at hospital discharge, clinical improvement at day 28 (WHO clinical progression scale), days spent in ICU, days spent in hospital after discharge from ICU, need for dialysis at day 28, bacterial superinfections, neutrophile to lymphocyte ratio, disease severity (CRP levels, PaO2/FiO2 ratio, D-dimer levels, fibrinogen, ferritin, PCT), adverse outcomes.
Hypothesis: patients receiving Vitamin D supplementation will have shorter number of days spent on mechanical ventilation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention | Experimental | Patients with low levels of Vitamin D on admission to ICU randomized to receive vitamin D supplementation |
|
| Control | No Intervention | Patients with low levels of Vitamin D on admission to ICU not receiving vitamin D supplementation |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cholecalciferol | Dietary Supplement | daily supplementation of cholecalciferol, 10 000 IU, during 14 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| number of days on mechanical ventilation | Number of days spent on mechanical ventilation for each patient | Daily, through study completion, on average 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| All-cause mortality on day 28 | Number of patients alive on day 28 | day 28 |
| All-cause mortality on day 60 | Number of patients alive on day 60 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lenko Saric, M.D. PhD | University Hospital Split, Croatia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Split | Split | 21000 | Croatia |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D012128 | Respiratory Distress Syndrome |
| D014808 | Vitamin D Deficiency |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| day 60 |
| clinical improvement at day 28 | World Health Organization Clinical progression scale. Values are from 0 to 10 with higher score meaning worse clinical status | day 28 |
| Number of days spent in ICU | Number of days spent in Intensive care unit for each patient | Daily, through study completion, on average 6 months |
| Number of days spent in hospital after ICU discharge | Number of days spent in hospital for each patient | Daily, through study completion, on average 6 months |
| Acute renal failure | Number of patients with need for renal replacement therapy | Day 28 |
| bacterial superinfections | Number of patients with bacterial superinfections during hospitalization | Daily, through study completion, on average 6 months |
| CRP levels (mg/ml) | blood tests will be taken daily during hospital stay | Daily, through study completion, on average 6 months |
| prokalcitonin levels (ng/ml) | blood tests will be taken daily during hospital stay | Daily, through study completion, on average 6 months |
| fibrinogen levels (g/L) | blood tests will be taken daily during hospital stay | Daily, through study completion, on average 6 months |
| D-dimer levels (mg/l) | blood tests will be taken daily during hospital stay | Daily, through study completion, on average 6 months |
| adverse outcomes | Number of patients with elevated serum calcium levels | Daily, through study completion, on average 6 months |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |