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

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01689441
• Collaborator: (none)
• Enrollment: 67
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 5.6

Study Details

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
• 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: Feb 1, 2013
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 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 [48 hours]

Secondary Outcome Measures

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

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Link to manuscript in pubmed

Publications

None provided.

• 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: Sep 21, 2012
• Last Update Posted: Nov 10, 2020
• Last Verified: Nov 1, 2020

• Additional relevant MeSH terms: Sepsis; Toxemia; Calcitriol

Study Results

Participant Flow

Arm/Group Title	Calcitriol	Placebo
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol	Normal saline 2cc IV x 1 Placebo
Period Title: Overall Study
STARTED	36	31
COMPLETED	36	31
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Calcitriol	Placebo	Total
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol	Normal saline 2cc IV x 1 Placebo	Total of all reporting groups
Overall Participants	36	31	67
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	68	58	64
Sex: Female, Male (Count of Participants)
Female	14 38.9%	16 51.6%	30 44.8%
Male	22 61.1%	15 48.4%	37 55.2%
Region of Enrollment (participants) [Number]
United States	36 100%	31 100%	67 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Calcitriol	Placebo
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol	Normal saline 2cc IV x 1 Placebo
Measure Participants	36	31
Median (Inter-Quartile Range) [ng/ml]	76	82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcitriol, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.25
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Plasma Interleukin-6 (IL-6) Levels at 48 Hours
Time Frame	48 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Calcitriol	Placebo
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol	Normal saline 2cc IV x 1 Placebo
Measure Participants	36	31
Median (Inter-Quartile Range) [pg/ml]	41	32

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcitriol, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Urinary Neutrophil Gelatinase-associated Lipocalin (NGAL) / Creatinine Ratio at 48 Hours
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Calcitriol	Placebo
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol	Normal saline 2cc IV x 1 Placebo
Measure Participants	30	24
Median (Inter-Quartile Range) [mg/mg]	0.6	0.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Calcitriol, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Calcitriol		Placebo
Arm/Group Description	Calcitriol 2mcg IV x 1 Calcitriol		Normal saline 2cc IV x 1 Placebo
All Cause Mortality
	Calcitriol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Calcitriol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Calcitriol		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.