Effect of high-dose vitamin D3 on 28-day mortality in adult critically ill patients with severe vitamin D deficiency: a study protocol of a multicentre, placebo-controlled double-blind phase III RCT (the VITDALIZE study)

Abstract

IntroductionObservational studies have demonstrated an association between vitamin D deficiency and increased risk of morbidity and mortality in critically ill patients. Cohort studies and pilot trials have suggested promising beneficial effects of vitamin D replacement in the critical ill, at least in patients with severe vitamin D deficiency. As vitamin D is a simple, low-cost and safe intervention, it has potential to improve survival in critically ill patients.Methods and analysisIn this randomised, placebo-controlled, double-blind, multicentre, international trial, 2400 adult patients with severe vitamin D deficiency (25-hydroxyvitamin D≤12 ng/mL) will be randomised in a 1:1 ratio by www.randomizer.at to receive a loading dose of 540 000 IU cholecalciferol within 72 hours after intensive care unit (ICU) admission, followed by 4000 IU daily for 90 days or placebo. Hypercalcaemia may occur as a side effect, but is monitored by regular checks of the calcium level. The primary outcome is all-cause mortality at 28 days after randomisation. Secondary outcomes are: ICU, hospital, 90-day and 1-year mortality; hospital and ICU length of stay, change in organ dysfunction on day 5 as measured by Sequential Organ Function Assessment (SOFA) score, number of organ failures; hospital and ICU readmission until day 90; discharge destination, self-reported infections requiring antibiotics until day 90 and health-related quality of life. Recruitment status is ongoing.Ethics and disseminationNational ethical approval was obtained by the Ethics Committee of the University of Graz for Austria, Erasme University Brussels (Belgium) and University Hospital Frankfurt (Germany), and will further be gained according to individual national processes. On completion, results will be published in a peer-reviewed scientific journal. The study findings will be presented at national and international meetings with abstracts online.Trial registration NCT03188796, EudraCT-No: 2016-002460-13.

Витамин D И Ожоговая Травма

“…Дефицит витамина D обычно определяется как уровень 25-гидроксивитамина D (25(OH)D) в сыворотке крови ниже 20 нг/мл (равно 50 нмоль/л) и отмечается у 40-70 % пациентов отделений реанимации и интенсив-Науковий огляд / Scientific Review В нескольких исследованиях было выявлено, что дефицит витамина D ассоциируется с большей тяжестью заболевания, вероятностью развития инфекционных осложнений, в том числе и сепсиса, развитием острой почечной, дыхательной недостаточности, более длительным проведением искусственной вентиляции легких, повышением времени пребывания как в стационаре, так и в ОРИТ, повышенным уровнем летальности у детей и у взрослых в критическом состоянии [1,3,8,9]. В настоящее время витамин D получает все более широкое признание благодаря своим обширным биологическим эффектам.…”

Controversies in Sepsis Management—What is the Way Forward?

“…A large RCT is currently looking at the use of high dose Vitamin D in critically ill patients with Vitamin D deficiency. 57…”

Metabolic and Endocrine Challenges

“…The difference was large (17.5%) and significant in the predefined subgroup of patients with severe vitamin D deficiency ( 88 As this was a secondary endpoint in the subgroup with severe deficiency, this finding is hypothesis generating leading to the currently recruiting international multicenter VITDALIZE trial. 89 Five trials are currently registered on clinicaltrials.gov examining vitamin D supplementation in the critically ill, including the VITDALIZE study. One is a phase II study in children (NCT02452762).…”