Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients

Sponsor

University Hospital of Split (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05384574

Collaborator

(none)

200

Enrollment

Location

Arms

7.3

Anticipated Duration (Months)

27.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Covid-19 Respiratory Distress Syndrome Vitamin D Deficiency	Dietary Supplement: cholecalciferol	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients - Randomized Controlled Trial

Actual Study Start Date :

Nov 22, 2021

Anticipated Primary Completion Date :

May 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Patients with low levels of Vitamin D on admission to ICU randomized to receive vitamin D supplementation	Dietary Supplement: cholecalciferol daily supplementation of cholecalciferol, 10 000 IU, during 14 days
No Intervention: Control Patients with low levels of Vitamin D on admission to ICU not receiving vitamin D supplementation

Arm

Intervention/Treatment

Experimental: Intervention

Patients with low levels of Vitamin D on admission to ICU randomized to receive vitamin D supplementation

Dietary Supplement: cholecalciferol

daily supplementation of cholecalciferol, 10 000 IU, during 14 days

No Intervention: Control

Patients with low levels of Vitamin D on admission to ICU not receiving vitamin D supplementation

Outcome Measures

Primary Outcome Measures

number of days on mechanical ventilation [Daily, through study completion, on average 6 months]
Number of days spent on mechanical ventilation for each patient

Secondary Outcome Measures

All-cause mortality on day 28 [day 28]
Number of patients alive on day 28
All-cause mortality on day 60 [day 60]
Number of patients alive on day 60
clinical improvement at day 28 [day 28]
World Health Organization Clinical progression scale. Values are from 0 to 10 with higher score meaning worse clinical status
Number of days spent in ICU [Daily, through study completion, on average 6 months]
Number of days spent in Intensive care unit for each patient
Number of days spent in hospital after ICU discharge [Daily, through study completion, on average 6 months]
Number of days spent in hospital for each patient
Acute renal failure [Day 28]
Number of patients with need for renal replacement therapy
bacterial superinfections [Daily, through study completion, on average 6 months]
Number of patients with bacterial superinfections during hospitalization
CRP levels (mg/ml) [Daily, through study completion, on average 6 months]
blood tests will be taken daily during hospital stay
prokalcitonin levels (ng/ml) [Daily, through study completion, on average 6 months]
blood tests will be taken daily during hospital stay
fibrinogen levels (g/L) [Daily, through study completion, on average 6 months]
blood tests will be taken daily during hospital stay
D-dimer levels (mg/l) [Daily, through study completion, on average 6 months]
blood tests will be taken daily during hospital stay
adverse outcomes [Daily, through study completion, on average 6 months]
Number of patients with elevated serum calcium levels

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

Patients will be excluded from study in case of calcium levels that are consistently above normal serum range (> 2.6 mmol/L, > 10.5 mg/dL) or if vitamin D levels are > 150 nmol/L.