Hypovitaminosis D in Neurocritical Patients

Phase 2

Completed

Conditions: Brain Neoplasms
Seizures
Meningitis
Stroke
Spinal Cord Injuries
Critical Illness
Craniocerebral Trauma
Intracranial Aneurysm
Vitamin d Deficiency
Intracranial Hemorrhages

Interventions: Other: Placebo
Drug: Cholecalciferol

Registration Number: NCT02881957

Lead Sponsor: University of Utah

Brief Summary: Vitamin D has been shown to impact prognosis in a variety of retrospective and randomized clinical trials within an intensive care unit (ICU) environment. Despite these findings, there have been no studies examining the impact of hypovitaminosis D in specialized neurocritical care units (NCCU). Given the often significant differences in the management of patients in NCCU and more generalized intensive care units there is a need for further inquiries into the impact of low vitamin D levels in this specific environment. This study proposes a randomized, double-blinded, placebo-controlled, single center evaluation of vitamin D supplementation in the emergent NCCU patient population. The primary outcome will involve length-of-stay for emergent neurocritical care patients. Various secondary outcomes, including in-hospital mortality, ICU length-of-stay, Glasgow Outcome Score on discharge, complications and quality-of-life metrics. Patients will be followed for 6 months post-discharge.

Detailed Description: Vitamin D has been shown as an important marker of prognosis in a variety of clinical settings, including overall mortality, acute respiratory distress syndrome (ARDS), infection/sepsis, asthma, cardiovascular disease, diabetes, and pediatric/medical/surgical intensive care unit outcomes. Vitamin D not only plays a role in bone maintenance, but also a variety of extra-axial functions including immune-dysregulation and systemic inflammation. In addition, a number of randomized clinical trials support the supplementation of vitamin D as improving outcome in critical care patients. While the evaluation of vitamin D levels remains a standard-of-care at our institution, the widespread use of vitamin D monitoring and impact on neurocritical care patients remains limited. The investigators' recent prospective observational study of vitamin D levels in neurocritical patients showed that deficiency (\<20ng/dL) was highly associated with prolonged hospital stay and increased in-hospital mortality for emergent patients. Moreover, a number of limitations arise from this study due to its observational nature. This study proposes a randomized, double-blinded, placebo-controlled, single center evaluation of vitamin D supplementation in the neurocritical care patient population. Patients admitted to the neurocritical care unit for emergent cases and with vitamin D deficiency (\<20ng/dL) will undergo vitamin D serum draw on admission and be randomized to receive cholecalciferol/vitamin D3 supplementation (540,000 IU once orally) or placebo. The primary outcome measured will be hospital length-of-stay. Secondary outcomes will include length of ICU course, complications, medication adverse events, discharge Glasgow Outcome Score, in-hospital and 30-day mortality, as well as quality-of-life. Power analysis estimates 198 patients will be needed for each subgroup to determine a 2 day difference in length-of-stay, and the study plans to recruit 218 patients per treatment arm to account for dropout, which will take approximately 6-9 months to recruit. Interim analysis and safety monitoring will be performed. The investigators hypothesize that vitamin D supplementation may make a significant impact on reducing morbidity and mortality in the neurocritical care population. The possibility of reducing hospital length of stay and mortality from a simple, safe, and cost-effective intervention such as vitamin D supplementation may be a useful adjuvant treatment in the neurocritical care population.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 274

Inclusion Criteria

Patients >18 years of age
Patients admitted to the neurosurgery or neurology services
Patients admitted to a critical care unit
Informed consent
Expected to stay in the ICU for 48 hours or more
Vitamin D deficiency (<20ng/mL)

Exclusion Criteria

Patients where a vitamin D level was not drawn within 48 hours of admission
Patients not randomized within 48 hours of admission
Readmitted patients to the critical care unit
Lack of informed consent
Prior supplementation with vitamin D
Severely impaired gastrointestinal function
Other trial participation
Pregnant or lactating women
Hypercalcemia (total calcium of >10.6 mg/dL or ionized serum calcium of >5.4 mg/dL
Tuberculosis history or clinical exam
Sarcoidosis history or clinical exam
Nephrolithiasis within the prior year
Patients not deemed suitable for study participation (ie, psychiatric disease, living remotely from the clinic, or prisoner status)
Pregnant or nursing women

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Placebo	Placebo control (simple oral syrup)
Vitamin D3	Cholecalciferol	Cholecalciferol/Vitamin D3 (540,000 IU orally or by feeding tube once)

Primary Outcome Measures

Name	Time	Method
Intent-to-treat Hospital Length-of-stay	Until discharge	Intent-to-treat hospital length-of-stay
As-treated Hospital Length of Stay	Until discharge	Two-sided t-test evaluated comparing length of stay in vitamin D3 vs. placebo treated patients utilizing patients after randomization, factoring excluded patients (e.g., as-treated) using a p\<0.05 as significant.

Secondary Outcome Measures

Name	Time	Method
Intent-to-treat ICU Length of Stay	Until discharge	Two-sided t-test evaluated comparing length of stay within the ICU specifically in vitamin D3 vs. placebo treated patients utilizing patients after randomization (e.g., intent-to-treat) using a p\<0.05 as significant.
As-treated ICU Length of Stay	Until discharge	Two-sided t-test evaluated comparing length of stay within the ICU specifically in vitamin D3 vs. placebo treated patients utilizing patients after randomization but excluding patients who did not receive treatment (e.g., as-treated) using a p\<0.05 as significant.
In-hospital Mortality	Until discharge	In-hospital mortality
Number of Participants With Study Drug Related Adverse Events	Until discharge	The occurrence of patients who suffered mortality, adverse events or severe adverse events, related specifically to the study drug was monitored. Severe adverse events are defined using common terminology criteria for adverse events (CTCAE) grade 3 or higher specific to vitamin D from time of study drug administration to discharge.
Number of Participants With Sepsis	Until discharge	Diagnosis of sepsis
Number of Participants With Pneumonia	Until discharge	Pneumonia diagnosis
Number of Participants With Urinary Tract Infection	Until discharge	Urinary tract infection diagnosis
Number of Participants With Deep Vein Thrombosis	Until discharge	Deep vein thrombosis diagnosis