Hypovitaminosis D in Neurocritical Patients

Stroke Clinical Trial

Official title:

Randomized Clinical Trial of Hypovitaminosis D Treatment in the Neurocritical Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02881957
• Other study ID #: IRB_00091541
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: October 10, 2016
• Est. completion date: October 10, 2018

Study information

• Verified date: May 2022
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 274
• Est. completion date: October 10, 2018
• Est. primary completion date: October 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aneurysm
• Avitaminosis
• Brain Neoplasms
• Craniocerebral Trauma
• Critical Illness
• Hemorrhage
• Intracranial Aneurysm
• Intracranial Hemorrhages
• Meningitis
• Rickets
• Seizures
• Spinal Cord Injuries
• Stroke
• Vitamin d Deficiency

Intervention

Drug:
• Cholecalciferol

Other:
• Placebo
Oral syrup placebo

Locations

Country	Name	City	State
United States	University of Utah Hospital	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

References & Publications (3)

Carter BS, Barker FG. Editorial. Choices in clinical trial design. J Neurosurg. 2019 Sep 13:1-3. doi: 10.3171/2019.7.JNS183276. [Epub ahead of print] — View 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. — View 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 13:1-10. doi: 10.3171/2018.11.JNS182713. [Epu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intent-to-treat Hospital Length-of-stay	Intent-to-treat hospital length-of-stay	Until discharge
Primary	As-treated Hospital Length of Stay	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.	Until discharge
Secondary	Intent-to-treat ICU Length of Stay	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.	Until discharge
Secondary	As-treated ICU Length of Stay	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.	Until discharge
Secondary	In-hospital Mortality	In-hospital mortality	Until discharge
Secondary	Number of Participants With Study Drug Related Adverse Events	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.	Until discharge
Secondary	Number of Participants With Sepsis	Diagnosis of sepsis	Until discharge
Secondary	Number of Participants With Pneumonia	Pneumonia diagnosis	Until discharge
Secondary	Number of Participants With Urinary Tract Infection	Urinary tract infection diagnosis	Until discharge
Secondary	Number of Participants With Deep Vein Thrombosis	Deep vein thrombosis diagnosis	Until discharge

External Links

•   University of Utah, Department of Neurosurgery