Trial Outcomes & Findings for Cholecalciferol Supplementation for Sepsis in the ICU (NCT NCT01896544)

Last Updated: 2016-06-13

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

30 participants

Primary outcome timeframe

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

Results posted on

2016-06-13

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Overall Study STARTED	10	10	10
Overall Study COMPLETED	10	10	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cholecalciferol Supplementation for Sepsis in the ICU

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Total n=30 Participants Total of all reporting groups
Age, Continuous	62 years n=5 Participants	65 years n=7 Participants	64 years n=5 Participants	64 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	30 participants n=4 Participants
Body mass index	30 kg/m^2 n=5 Participants	28 kg/m^2 n=7 Participants	28 kg/m^2 n=5 Participants	28 kg/m^2 n=4 Participants
Acute Physiology and Chronic Health Evaluation II (APACHE II) score	23 scores on a scale n=5 Participants	22 scores on a scale n=7 Participants	21 scores on a scale n=5 Participants	22 scores on a scale n=4 Participants
Intensive Care Unit (ICU) type medical	5 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	16 participants n=4 Participants
Intensive Care Unit (ICU) type surgical	5 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	14 participants n=4 Participants
Positive culture Pulmonary	40 percentage n=5 Participants	40 percentage n=7 Participants	50 percentage n=5 Participants	130 percentage n=4 Participants
Positive culture Blood stream	70 percentage n=5 Participants	60 percentage n=7 Participants	60 percentage n=5 Participants	190 percentage n=4 Participants
Positive culture Urinary	10 percentage n=5 Participants	10 percentage n=7 Participants	10 percentage n=5 Participants	30 percentage n=4 Participants
Day 1 data: 25 hydroxyvitaminD(25OHD),bioavailable 25 hydroxyvitamin D(B25OHD), cathelicidin (LL-37) Day 1 25OHD (ng/mL)	17 ng/mL n=5 Participants	19 ng/mL n=7 Participants	15 ng/mL n=5 Participants	17 ng/mL n=4 Participants
Day 1 data: 25 hydroxyvitaminD(25OHD),bioavailable 25 hydroxyvitamin D(B25OHD), cathelicidin (LL-37) Day 1 B25OHD (ng/mL)	2.5 ng/mL n=5 Participants	1.4 ng/mL n=7 Participants	1.9 ng/mL n=5 Participants	1.9 ng/mL n=4 Participants
Day 1 data: 25 hydroxyvitaminD(25OHD),bioavailable 25 hydroxyvitamin D(B25OHD), cathelicidin (LL-37) Day 1 LL-37 (ng/mL)	51 ng/mL n=5 Participants	53 ng/mL n=7 Participants	52 ng/mL n=5 Participants	52 ng/mL n=4 Participants
30 day readmission No	10 participants n=5 Participants	8 participants n=7 Participants	10 participants n=5 Participants	28 participants n=4 Participants
30 day readmission Yes	0 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
30 day mortality dead	2 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	8 participants n=4 Participants
30 day mortality alive	8 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	22 participants n=4 Participants
Day 1 data: high-sensitivity c-reactive protein (hs-CRP)	119 mg/L n=5 Participants	106 mg/L n=7 Participants	208 mg/L n=5 Participants	119 mg/L n=4 Participants
Day 1: total body fluid balance (TBB)	1,518 mL n=5 Participants	1592 mL n=7 Participants	1,730 mL n=5 Participants	1,592 mL n=4 Participants

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Change in Vitamin D Status 5 Days Following Supplementation With Cholecalciferol Day 5	19 ng/mL Interval 11.0 to 23.0	22 ng/mL Interval 16.0 to 25.0	29 ng/mL Interval 23.0 to 41.0
Change in Vitamin D Status 5 Days Following Supplementation With Cholecalciferol Day 1	19 ng/mL Interval 13.0 to 22.0	15 ng/mL Interval 12.0 to 20.0	17 ng/mL Interval 13.0 to 25.0

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol Day 1 LL-37 (ng/mL)	53 ng/mL Interval 43.0 to 62.0	52 ng/mL Interval 48.0 to 59.0	51 ng/mL Interval 41.0 to 52.0
Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol Day 5 LL 37 (ng/mL)	50 ng/mL Interval 35.0 to 54.0	54 ng/mL Interval 40.0 to 64.0	67 ng/mL Interval 59.0 to 68.0

SECONDARY outcome

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

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. The incidence of infection-related complications will be assessed between the onset of suspected sepsis and 80-100 days after supplementation with cholecalciferol or placebo. To assess the incidence of infection-related complications, we will measure rates of: 1) ICU length of stay; and 2) hospital length of stay

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis ICU length of stay	12 days Interval 7.0 to 15.0	4 days Interval 3.0 to 11.0	3 days Interval 2.0 to 11.0
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis Hospital length of stay	21 days Interval 18.0 to 31.0	13 days Interval 12.0 to 16.0	14 days Interval 8.0 to 21.0

SECONDARY outcome

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

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. The incidence of infection-related complications will be assessed between the onset of suspected sepsis and 80-100 days after supplementation with cholecalciferol or placebo. To assess the incidence of infection-related complications, we will measure rates of: 1\) 30 day hospital readmission; and 2) 30 day mortality.

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis 30 day readmission: no	8 participants	10 participants	10 participants
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis 30 day readmission: yes	2 participants	0 participants	0 participants
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis 30 day mortality: dead	3 participants	3 participants	2 participants
Incidence of Infection-related Complications Within 90 Days From the Onset of a Suspected Case of Sepsis 30 day mortality:alive	7 participants	7 participants	8 participants

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Placebo n=10 Participants Oral suspension of placebo cholecalciferol Placebo: 7ml syringe of placebo cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose I n=10 Participants Oral suspension cholecalciferol 200,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube	Cholecalciferol Dose II n=10 Participants Oral suspension cholecalciferol 400,000 IU Cholecalciferol: 7ml syringe of cholecalciferol suspension given through NG or OG tube
Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol Day 1 hsCRP (mg/L)	106 mg/L Interval 60.0 to 267.0	208 mg/L Interval 90.0 to 369.0	119 mg/L Interval 85.0 to 247.0
Change in Immunological Profile 5 Days Following Supplementation With Cholecalciferol D 5 hsCRP (mg/L)	53 mg/L Interval 38.0 to 72.0	98 mg/L Interval 12.0 to 130.0	31 mg/L Interval 26.0 to 160.0

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cholecalciferol Dose I

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cholecalciferol Dose II

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Tiffany M.N. Otero

Massachusetts General hospital

Phone: 4074950753

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place