Randomized Controlled Trial of Calcitriol vs. Placebo Among Critically-ill Patients With Sepsis

Overview

Observational studies among critically ill patients have shown strong associations between vitamin D deficiency and adverse outcomes, including increased length of stay, infection, and mortality. It is unknown whether vitamin D deficiency contributes directly to adverse outcomes or whether it is simply a biomarker of severity of illness or overall health status. However, vitamin D plays a key role in host defense, largely by stimulating production of the anti-microbial peptide cathelicidin (LL-37). We will test the hypothesis that administration of activated vitamin D (calcitriol) will increase serum levels of cathelicidin.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 2014

Interventions

  • Drug: Calcitriol
  • Drug: Placebo

Arms, Groups and Cohorts

  • Experimental: Calcitriol
    • Calcitriol 2mcg IV x 1
  • Placebo Comparator: Placebo
    • Normal saline 2cc IV x 1

Clinical Trial Outcome Measures

Primary Measures

  • Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours
    • Time Frame: 48 hours

Secondary Measures

  • Plasma Interleukin-6 (IL-6) Levels at 48 Hours
    • Time Frame: 48 hours
  • Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 48 Hours
    • Time Frame: 48 hours
    • NGAL is a urinary marker of renal tubular injury. NGAL levels were normalized to the urinary creatinine concentration to account for the influence of dilution on biomarker concentrations.

Participating in This Clinical Trial

Inclusion Criteria

  • age ≥ 18 – Severe sepsis or septic shock – Central venous catheter (for blood drawing) Exclusion Criteria:

  • Serum calcium ≥ 10.0 mg/dl or phosphate ≥ 6.0 mg/dl, assessed within previous 48 hours – Current or recent therapy (within previous 7 days) with nutritional vitamin D at doses >1,000 I.U. per day or activated vitamin D at any dose – History of solid organ or bone marrow transplant, primary parathyroid disease, metabolic bone disease, or sarcoidosis – Expected to die or leave the ICU within 48 hours – History of hypersensitivity or any allergic reaction to calcitriol – End stage renal disease – Acute Kidney Injury receiving intermittent renal replacement therapy – Enrolled in a competing study – Pregnancy

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Brigham and Women’s Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: David Leaf, Assistant Professor of Medicine, Harvard Medical School – Brigham and Women’s Hospital
  • Overall Official(s)
    • David E Leaf, M.D., Principal Investigator, Brigham and Women’s Hospital

Citations Reporting on Results

Leaf DE, Raed A, Donnino MW, Ginde AA, Waikar SS. Randomized controlled trial of calcitriol in severe sepsis. Am J Respir Crit Care Med. 2014 Sep 1;190(5):533-41. doi: 10.1164/rccm.201405-0988OC.

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