Cholecalciferol Supplementation for Sepsis in the ICU

NCT01896544 | Completed Phase 3 Results DMC

• 1 other identifier: 2013P001406
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypovitaminosis D

Keywords

cholecalciferol; vitamin D; sepsis; infection

Outcome Measures

Primary Outcomes (1)

• Change in Vitamin D Status 5 Days Following Supplementation With Cholecalciferol

  Subjects will receive 200,000 IU or 400,000 IU cholecalciferol suspension (vs. placebo) within 24 hours from the onset of a suspected case of sepsis during their hospitalization. Vitamin D status at the onset of a suspected case of sepsis will be compared to vitamin D status between 5-9 days after supplementation with cholecalciferol or placebo. To assess vitamin D status, we will measure serum and urine: 1) 25-hydroxyvitamin D; 2) 1,25-dihydroxyvitamin D; 3) 24,25-dihydroxyvitamin D; 4) Fibroblast growth factor 23; 5) Vitamin D binding protein; 6) LL-37; 7) Parathyroid hormone; 8) Albumin; 9) Calcium; and 10) Phosphorus levels.

  Patients will be followed between the onset of suspected sepsis and for an average duration of 7 days

Secondary Outcomes (4)

• Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol

  Patients will be followed between the onset of suspected sepsis and for an average duration of 7 days

• Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis

  Patients will be followed between the onset of suspected sepsis and for an average duration of 90 days

• Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis

  Patients will be followed between the onset of suspected sepsis and for an average duration of 90 days

• Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol

  Patients will be followed between the onset of suspected sepsis and for an average duration of 90 days

Study Arms (3)

Cholecalciferol Dose II

ACTIVE COMPARATOR

Oral suspension cholecalciferol 400,000 IU

Dietary Supplement: Cholecalciferol

Placebo

PLACEBO COMPARATOR

Oral suspension of placebo cholecalciferol

Dietary Supplement: Placebo

Cholecalciferol Dose I

ACTIVE COMPARATOR

Oral suspension cholecalciferol 200,000 IU

Dietary Supplement: Cholecalciferol

Interventions

Cholecalciferol DIETARY_SUPPLEMENT

7ml syringe of cholecalciferol suspension given through nasogastric (NG) or orogastric (OG) tube

Cholecalciferol Dose I; Cholecalciferol Dose II

Placebo DIETARY_SUPPLEMENT

7ml syringe of placebo cholecalciferol suspension given through nasogastric (NG) or orogastric (OG) tube

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Vital signs:
• Temperature: \>38.3 Celsius (C) or \<36 Celsius (C)
• Heart rat e: \>90/min, or \>2 standard deviation above normal
• Tachypnea (\>20 breaths per minute)
• Altered mental status
• Positive fluid balance (\>20 mL/Kg over 24 hrs)
• Glucose \>140 mg/dL in the absence of diabetes mellitus
• Inflammatory markers:
• white blood cell (WBC): \>12,000 or \<4,000
• Normal WBC count with \>10% immature forms
• c-reactive protein (CRP) \>2 standard deviation above normal value
• Pro- calcitonin \>2 standard deviation above normal value

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Vitamin D Deficiency; Sepsis; Infections

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Tiffany M.N. Otero
• Organization: Massachusetts General hospital

totero@partners.org

4074950753

Study Officials

• Sadeq A Quraishi, MD, MHA, MMSc

  Harvard Medical School, Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anaesthesia, Harvard Medical School

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: January 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 13, 2016
• Results First Posted: June 13, 2016

Record last verified: 2016-05

Locations

US (1)