Severe Sepsis or Septic Shock
Conditions
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.
Interventions
DRUGCalcitriol
DRUGPlacebo
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours | 48 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Interleukin-6 (IL-6) Levels at 48 Hours | 48 hours | — |
| Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 48 Hours | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Calcitriol Calcitriol 2mcg IV x 1
Calcitriol | 36 |
| Placebo Normal saline 2cc IV x 1
Placebo | 31 |
| Total | 67 |
Baseline characteristics
| Characteristic | Calcitriol | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 68 years | 58 years | 64 years |
| Region of Enrollment United States | 36 participants | 31 participants | 67 participants |
| Sex: Female, Male Female | 14 Participants | 16 Participants | 30 Participants |
| Sex: Female, Male Male | 22 Participants | 15 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 36 | 0 / 31 |
| serious Total, serious adverse events | 0 / 36 | 0 / 31 |
Outcome results
Primary
Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Calcitriol | Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours | 76 ng/ml |
| Placebo | Plasma Cathelicidin (hCAP18) Protein Levels at 48 Hours | 82 ng/ml |
p-value: 0.25Wilcoxon (Mann-Whitney)
Secondary
Plasma Interleukin-6 (IL-6) Levels at 48 Hours
Time frame: 48 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Calcitriol | Plasma Interleukin-6 (IL-6) Levels at 48 Hours | 41 pg/ml |
| Placebo | Plasma Interleukin-6 (IL-6) Levels at 48 Hours | 32 pg/ml |
p-value: 0.51Wilcoxon (Mann-Whitney)
Secondary
Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 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.
Time frame: 48 hours
Population: The discrepancy in number of participants analyzed for this outcome vs. other outcomes is due to urine samples not being available in all participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Calcitriol | Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 48 Hours | 0.6 mg/mg |
| Placebo | Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 48 Hours | 0.7 mg/mg |
p-value: 0.54Wilcoxon (Mann-Whitney)