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

• ClinicalTrials.gov Identifier: NCT01689441
• Recruitment Status: Completed
• First Posted: September 21, 2012
• Results First Posted: October 30, 2014
• Last Update Posted: November 10, 2020
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): David Leaf, Brigham and Women's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Severe Sepsis or Septic Shock	Drug: Calcitriol; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 67 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Calcitriol vs. Placebo Among Critically-ill Patients With Sepsis
• Study Start Date: February 2013
• Actual Primary Completion Date: February 2014
• Actual Study Completion Date: February 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Calcitriol; Calcitriol 2mcg IV x 1	Drug: Calcitriol
Placebo Comparator: Placebo; Normal saline 2cc IV x 1	Drug: Placebo

Outcome Measures

Primary Outcome Measures :

1. Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours [ Time Frame: 48 hours ]

Secondary Outcome Measures :

1. Plasma Interleukin-6 (IL-6) Levels at 48 Hours [ Time Frame: 48 hours ]
2. 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.

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:

• 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

Contacts and Locations

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

• Principal Investigator: David E Leaf, M.D.; Brigham and Women's Hospital

More Information

Additional Information:

Link to manuscript in pubmed 

Publications of 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.

• Responsible Party: David Leaf, Assistant Professor of Medicine, Harvard Medical School, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01689441
• Other Study ID Numbers: 2012P001755
• First Posted: September 21, 2012
• Results First Posted: October 30, 2014
• Last Update Posted: November 10, 2020
• Last Verified: November 2020

Additional relevant MeSH terms:

Sepsis; Toxemia; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Calcitriol; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Calcium Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents; Vitamins; Micronutrients; Bone Density Conservation Agents