Hypovitaminosis D in Neurocritical Patients

• ClinicalTrials.gov Identifier: NCT02881957
• Recruitment Status: Completed
• First Posted: August 29, 2016
• Results First Posted: August 17, 2020
• Last Update Posted: August 17, 2020
• Sponsor: University of Utah
• Information provided by (Responsible Party): Michael Karsy, MD, PhD, MSC, University of Utah

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Craniocerebral Trauma; Intracranial Aneurysm; Brain Neoplasms; Spinal Cord Injuries; Seizures; Meningitis; Stroke; Intracranial Hemorrhages; Critical Illness; Vitamin d Deficiency	Drug: Cholecalciferol; Other: Placebo	Phase 2; Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 274 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Clinical Trial of Hypovitaminosis D Treatment in the Neurocritical Care Unit
• Actual Study Start Date: October 10, 2016
• Actual Primary Completion Date: October 10, 2018
• Actual Study Completion Date: October 10, 2018

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Control; Placebo control (simple oral syrup)	Other: Placebo; Oral syrup placebo
Experimental: Vitamin D3; Cholecalciferol/Vitamin D3 (540,000 IU orally or by feeding tube once)	Drug: Cholecalciferol; Other Name: vitamin D3

Outcome Measures

Primary Outcome Measures :

1. Intent-to-treat Hospital Length-of-stay [ Time Frame: Until discharge ]
   Intent-to-treat hospital length-of-stay
2. As-treated Hospital Length of Stay [ Time Frame: 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 :

1. Intent-to-treat ICU Length of Stay [ Time Frame: 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.
2. As-treated ICU Length of Stay [ Time Frame: 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.
3. In-hospital Mortality [ Time Frame: Until discharge ]
   In-hospital mortality
4. Number of Participants With Study Drug Related Adverse Events [ Time Frame: 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.
5. Number of Participants With Sepsis [ Time Frame: Until discharge ]
   Diagnosis of sepsis
6. Number of Participants With Pneumonia [ Time Frame: Until discharge ]
   Pneumonia diagnosis
7. Number of Participants With Urinary Tract Infection [ Time Frame: Until discharge ]
   Urinary tract infection diagnosis
8. Number of Participants With Deep Vein Thrombosis [ Time Frame: Until discharge ]
   Deep vein thrombosis diagnosis

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Utah

University of Utah Hospital

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

University of Utah

Investigators

• Principal Investigator: Michael Karsy, MD, PhD; University of Utah, Department of Neurosurgery, Salt Lake City, UT
• Study Director: Min S Park, MD; University of Utah, Department of Neurosurgery, Salt Lake City, UT

  Study Documents (Full-Text)

Documents provided by Michael Karsy, MD, PhD, MSC, University of Utah:

Informed Consent Form  [PDF] September 13, 2017

Study Protocol and Statistical Analysis Plan  [PDF] August 30, 2017

More Information

Additional Information:

University of Utah, Department of Neurosurgery 

Publications of Results:

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. [Epub ahead of print]

Other Publications:

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.

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]

• Responsible Party: Michael Karsy, MD, PhD, MSC, M.D. Ph.D., University of Utah
• ClinicalTrials.gov Identifier: NCT02881957
• Other Study ID Numbers: IRB_00091541
• First Posted: August 29, 2016
• Results First Posted: August 17, 2020
• Last Update Posted: August 17, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Michael Karsy, MD, PhD, MSC, University of Utah:

critical illness; craniocerebral trauma; intracranial aneurysm; spinal cord injuries; seizures; meningitis; stroke; vitamin d deficiency; cholecalciferol; intracranial hemorrhages

Additional relevant MeSH terms:

Brain Neoplasms; Rickets; Spinal Cord Injuries; Seizures; Meningitis; Intracranial Aneurysm; Intracranial Hemorrhages; Craniocerebral Trauma; Aneurysm; Vitamin D Deficiency; Avitaminosis; Hemorrhage; Critical Illness; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Spinal Cord Diseases; Trauma, Nervous System; Wounds and Injuries; Neurologic Manifestations; Disease Attributes; Deficiency Diseases; Malnutrition; Nutrition Disorders; Intracranial Arterial Diseases; Central Nervous System Neoplasms