Hypovitaminosis D in Neurocritical Patients

Utah System of Higher Education (USHE)

Status and phase: Completed; Phase 3; Phase 2

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

Treatments: Other: Placebo; Drug: Cholecalciferol

Study type: Interventional

Funder types: Other

Identifiers

NCT02881957

IRB_00091541

Details and patient eligibility

About

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.

Full 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.

Enrollment: 274 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

274 participants in 2 patient groups, including a placebo group

Control

Placebo Comparator group

Description:

Placebo control (simple oral syrup)

Treatment:

Other: Placebo

Vitamin D3

Experimental group

Description:

Cholecalciferol/Vitamin D3 (540,000 IU orally or by feeding tube once)

Treatment:

Drug: Cholecalciferol