Clinical trial NCT02881957: Hypovitaminosis D in Neurocritical Patients
Official title: Randomized Clinical Trial of Hypovitaminosis D Treatment in the Neurocritical Care Unit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Craniocerebral Trauma
Intracranial Aneurysm
Brain Neoplasms
Spinal Cord Injuries
Seizures
Meningitis
Stroke
Intracranial Hemorrhages
Critical Illness
Vitamin d Deficiency
Keywords: critical illness
craniocerebral trauma
intracranial aneurysm
spinal cord injuries
seizures
meningitis
stroke
vitamin d deficiency
cholecalciferol
intracranial hemorrhages
Lead sponsor: University of Utah
Sponsor class: OTHER
First posted: 2016-08-29
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intent-to-treat Hospital Length-of-stay
timeFrame: Until discharge
measure: As-treated Hospital Length of Stay
timeFrame: Until discharge
Secondary outcomes:
measure: Intent-to-treat ICU Length of Stay
timeFrame: Until discharge
measure: As-treated ICU Length of Stay
timeFrame: Until discharge
measure: In-hospital Mortality
timeFrame: Until discharge
measure: Number of Participants With Study Drug Related Adverse Events
timeFrame: Until discharge
measure: Number of Participants With Sepsis
timeFrame: Until discharge
measure: Number of Participants With Pneumonia
timeFrame: Until discharge
measure: Number of Participants With Urinary Tract Infection
timeFrame: Until discharge
measure: Number of Participants With Deep Vein Thrombosis
timeFrame: Until discharge
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
Study officials:
affiliation: University of Utah, Department of Neurosurgery, Salt Lake City, UT
name: Michael Karsy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah, Department of Neurosurgery, Salt Lake City, UT
name: Min S Park, MD
role: STUDY_DIRECTOR
References:
citation: Guan J, Karsy M, Brock AA, Eli IM, Ledyard HK, Hawryluk GWJ, Park MS. A prospective analysis of hypovitaminosis D and mortality in 400 patients in the neurocritical care setting. J Neurosurg. 2017 Jul;127(1):1-7. doi: 10.3171/2016.4.JNS16169. Epub 2016 Jul 1.
citation: Carter BS, Barker FG. Editorial. Choices in clinical trial design. J Neurosurg. 2019 Sep 13;133(4):1100-1102. doi: 10.3171/2019.7.JNS183276. Print 2020 Oct 1. No abstract available.
citation: Karsy M, Guan J, Eli I, Brock AA, Menacho ST, Park MS. The effect of supplementation of vitamin D in neurocritical care patients: RandomizEd Clinical TrIal oF hYpovitaminosis D (RECTIFY). J Neurosurg. 2019 Sep 13;133(4):1103-1112. doi: 10.3171/2018.11.JNS182713. Print 2020 Oct 1.