Cholecalciferol Supplementation for Sepsis in the ICU
Condition: Hypovitaminosis D
MeSH terms: Sepsis; Rickets; Avitaminosis; Vitamin D Deficiency
Intervention: Cholecalciferol; Placebo
Intervention description: 7ml syringe of cholecalciferol suspension given through nasogastric (NG) or orogastric (OG) tube; 7ml syringe of placebo cholecalciferol suspension given through nasogastric (NG) or orogastric (OG) tube
Intervention MeSH terms: Cholecalciferol; Vitamin D
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: cholecalciferol; vitamin D; sepsis; infection

Summary:

      Sepsis in a clinical entity that occurs in patients with serious infections. Though the
      severity of illness may vary, every year, approximately 1.6 million Americans are treated for
      sepsis. Even with timely interventions, anywhere from 16% to >80% of patients with sepsis
      will not survive. Immune dysfunction is thought to play a critical role in the ability for
      infections to evolve into sepsis and to eventually lead to death. Recently, vitamin D has
      been identified as a key regulator of the immune system. While it remains unclear whether
      optimizing vitamin D status may improve outcomes in sepsis, little is known about the effects
      of vitamin D supplementation in patients with severe infections. As such, our goal is to
      study whether high doses of cholecalciferol (vitamin D3) can improve vitamin D status and
      boost certain aspects of the immune system in patients with sepsis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  English or Spanish speaking

          -  Within 24 hours of a suspected diagnosis of sepsis

          -  Meeting criteria for sepsis (defined as suspected or confirmed infection AND at least
             one diagnostic criteria in each of the following groupings):

               1. Vital signs:

                    1. Temperature: >38.3 Celsius (C) or <36 Celsius (C)

                    2. Heart rat e: >90/min, or >2 standard deviation above normal

                    3. Tachypnea (>20 breaths per minute)

                    4. Altered mental status

                    5. Positive fluid balance (>20 mL/Kg over 24 hrs)

                    6. Glucose >140 mg/dL in the absence of diabetes mellitus

               2. Inflammatory markers:

                    1. white blood cell (WBC): >12,000 or <4,000

                    2. Normal WBC count with >10% immature forms

                    3. c-reactive protein (CRP) >2 standard deviation above normal value

                    4. Pro- calcitonin >2 standard deviation above normal value

               3. Hemodynamic

                    1. Systolic blood pressure (SBP) <90 millimeters mercury (mmHg), Mean Arterial
                       Pressure (MAP) <70mmHg or SBP decrease >40mmHg

                    2. Vasopressor therapy to maintain MAP >65mmHg

               4. Organ dysfunction

                    1. Arterial hypoxemia arterial oxygen partial pressure/fractional inspired
                       oxygen (PaO2/FiO2) <300

                    2. Acute Oliguria (UoP <0.5 mL/Kg/hr for at least 2 hours)

                    3. Cr increase >0.5 mg/dL

                    4. Coagulopathy: internationals normalized ratio (INR) >1.5 or a-partial
                       prothrombin time (aPTT) >60 sec

                    5. Thrombocytopenia: Platelet (PLT) <100 thousand (K)

                    6. Hyperbilirubinemia: Total Bilirubin (Tbili) >4 mg/dL

               5. Tissue perfusion

                    1. Lactate >2 mmol/L

                    2. Decrease cap refill or mottling

        Exclusion Criteria:

          -  Pregnant females or immediate post-partum status

          -  "Comfort measures only" status

          -  Inability to provide informed consent or have a surrogate consent

          -  History of renal stones within the past year

          -  History of hypercalcemia within the past year

          -  Baseline serum total calcium >10 mg/dL

          -  Established diagnosis associated with increased risk of hypercalcemia (e.g. metastatic
             cancer, sarcoidosis, multiple myeloma, primary hyperparathyroidism)

          -  History of severe anemia (Hematocrit <25%)

          -  Medications that affect vitamin D metabolism (e.g. antiepileptics, tuberculosis
             medication

          -  Already enrolled or planning to enroll in a research study that would conflict with
             full participation in the current study or confound the observation or interpretation
             of the study findings