Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03096314
Recruitment Status : Completed
First Posted : March 30, 2017
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Boyd Taylor Thompson, Massachusetts General Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Acute Respiratory Distress Syndrome
Vitamin D Deficiency
Critical Illness
Interventions Drug: Vitamin D3
Drug: Placebo
Enrollment 1358
Recruitment Details  
Pre-assignment Details After initial study screening, eligible patients were consented and received secondary screening for vitamin D deficiency; performed via an FDA-approved test (either hospital clinical laboratory or the FastPack IP device (Qualigen Inc., Carlsbad, CA). Participants with a screening 25OHD level <20 ng/mL were randomized for treatment assignment.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description Patients at high risk for ARDS and mortality with initial screening 25OHD levels < 20 ng/mL randomized to receive 540,00 IU vitamin D3 (cholecalciferol) as a single, liquid enteral dose, administered either orally or via naso/orogastric tube within 2 hours of randomization. Patients at high risk for ARDS and mortality with initial screening 25OHD levels < 20 ng/mL randomized to receive placebo (similar in appearance to the vitamin D3 treatment) as a single, liquid enteral dose, administered either orally or via naso/orogastric tube within 2 hours of randomization.
Period Title: Screened Vitamin D Deficient
Started 690 668 [1]
Completed 681 656
Not Completed 9 12
Reason Not Completed
Lost to Follow-up             9             12
[1]
2 randomized but not included in analysis; 1 treated but inadequate consent and 1 withdrew.
Period Title: Confirmed Vitamin D Deficient
Started 538 [1] 540 [1]
Completed 531 528
Not Completed 7 12
[1]
Confirmed deficient (a prior primary analysis subgroup) is a subgroup of the screened deficient.
Arm/Group Title High Dose Vitamin D Formulation Placebo Total
Hide Arm/Group Description

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Total of all reporting groups
Overall Number of Baseline Participants 538 540 1078
Hide Baseline Analysis Population Description
There were 1360 patients who screened as vitamin D deficient (all randomized) and received a confirmatory LC/MS/MS test (liquid chromatography tandem mass spectrometry). Subjects with a 25OHD result <20 ng/L by LC/MS/MS were the confirmed deficient cohort and included in the primary analysis (N= 538 in Vit D Arm and N = 540 in Placebo arm).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
<=18 years
1
   0.2%
0
   0.0%
1
   0.1%
Between 18 and 65 years
368
  68.4%
379
  70.2%
747
  69.3%
>=65 years
169
  31.4%
161
  29.8%
330
  30.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
Female
229
  42.6%
238
  44.1%
467
  43.3%
Male
309
  57.4%
302
  55.9%
611
  56.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/Ethnicity Number Analyzed 538 participants 540 participants 1078 participants
Non-Hispanic White
280
  52.0%
287
  53.1%
567
  52.6%
Black
130
  24.2%
122
  22.6%
252
  23.4%
Non-Black Hispanic
33
   6.1%
31
   5.7%
64
   5.9%
Other
15
   2.8%
12
   2.2%
27
   2.5%
Not Available
80
  14.9%
88
  16.3%
168
  15.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 538 participants 540 participants 1078 participants
538 540 1078
Facility residence prior to hospitalization (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
33
   6.1%
35
   6.5%
68
   6.3%
Health-related quality of life by EuroQol (EQ-5D-5L)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 538 participants 540 participants 1078 participants
0.7  (0.3) 0.7  (0.3) 0.7  (0.3)
[1]
Measure Description: The questionnaire provides a simple descriptive profile of a respondent’s health state. Index ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health)
Charlson co-morbidity index   [1] 
Mean (Standard Deviation)
Unit of measure:  Index
Number Analyzed 538 participants 540 participants 1078 participants
4.0  (2.9) 3.5  (6.5) 3.7  (2.9)
[1]
Measure Description: The Charlson comorbidity index predicts the one-year mortality for a patient who may have a range of comorbid conditions, such as heart disease, AIDS, or cancer (a total of 22 conditions). Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. Index scores range from 0 to 37, with higher scores indicating more coexisting conditions.
Body mass index (BMI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 524 participants 529 participants 1053 participants
29.8  (10.1) 31.0  (11.4) 30.4  (10.8)
[1]
Measure Analysis Population Description: Data missing on some subjects prevented calculating index on total cohort.
Lung Injury risk factors number (%)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Pneumonia Number Analyzed 538 participants 540 participants 1078 participants
204
  37.9%
181
  33.5%
385
  35.7%
Shock Number Analyzed 538 participants 540 participants 1078 participants
192
  35.7%
197
  36.5%
389
  36.1%
Sepsis Number Analyzed 538 participants 540 participants 1078 participants
185
  34.4%
174
  32.2%
359
  33.3%
mechanical ventilation for acute resp failure Number Analyzed 538 participants 540 participants 1078 participants
119
  22.1%
121
  22.4%
240
  22.3%
Aspiration Number Analyzed 538 participants 540 participants 1078 participants
27
   5.0%
35
   6.5%
62
   5.8%
Lung contusion Number Analyzed 538 participants 540 participants 1078 participants
15
   2.8%
18
   3.3%
33
   3.1%
Pancreatitis Number Analyzed 538 participants 540 participants 1078 participants
17
   3.2%
19
   3.5%
36
   3.3%
[1]
Measure Description: Subjects may have more than one risk factor
Medical intensive care unit admission - (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
447
  83.1%
462
  85.6%
909
  84.3%
Total Sequential Organ Failure Assessment (SOFA) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 538 participants 540 participants 1078 participants
4.1  (2.9) 4.0  (3.1) 4  (3)
[1]
Measure Description: The Sequential Organ Failure Assessment (SOFA) Score is a mortality prediction score that is based on the degree of dysfunction of six organ systems. The score is calculated on admission and every 24 hours until discharge using the worst parameters measured during the prior 24 hours. The score ranges from 0-24; a higher score indicates greater predicted mortality.
Lung injury prediction score (LIPS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Score
Number Analyzed 538 participants 540 participants 1078 participants
5.3  (2.9) 5.3  (3.1) 5.3  (3)
[1]
Measure Description: The lung injury prediction score (LIPS) is a validated prediction model that uses clinical data at the time of presentation to the emergency department (ED) to identify patients at high risk for ARDS. The score is a sum of 19 components, each of which is assigned points. A score of zero = no lung injury. Missing values are given a value of zero. The score ranges from 0 to 36, with higher scores indicating a higher risk of lung injury (as described in Gajic AJRCCM 2020; PMID 20802164).
Mechanical Ventilation (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
173
  32.2%
184
  34.1%
357
  33.1%
ARDS (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
44
   8.2%
44
   8.1%
88
   8.2%
Vasopressor use at baseline (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
169
  31.4%
177
  32.8%
346
  32.1%
Vitamin D supplement use in past week (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
31
   5.8%
24
   4.4%
55
   5.1%
Multivitamin use in past week (%)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 538 participants 540 participants 1078 participants
38
   7.1%
37
   6.9%
75
   7.0%
Estimated average daily vitamin D dose   [1] 
Mean (Standard Deviation)
Unit of measure:  IU
Number Analyzed 57 participants 54 participants 111 participants
3269  (13118) 4252  (15094) 3747.1  (14057.7)
[1]
Measure Analysis Population Description: This variable was analyzed in those participants that received a multivitamin/supplement within 30 days prior to current study hospitalization.
25-hydroxyvitamin D  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 538 participants 540 participants 1078 participants
11.2  (4.8) 11  (4.7) 11.1  (4.7)
Total serum calcium (mg/dL)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 528 participants 526 participants 1054 participants
8.3  (0.9) 8.3  (0.9) 8.3  (0.9)
[1]
Measure Analysis Population Description: This outcome was analyzed in participants in the confirmed deficient cohort with available serum calcium levels.
Ionized calcium (mg/dL)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 210 participants 212 participants 422 participants
4.3  (1.4) 4.3  (0.9) 4.3  (1.2)
[1]
Measure Analysis Population Description: This outcome was analyzed in participants in the confirmed deficient cohort with available ionized calcium levels.
Creatinine (mg/dL)   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 535 participants 539 participants 1074 participants
2.2  (2.3) 2.0  (2.0) 2.1  (2.2)
[1]
Measure Analysis Population Description: This outcome was analyzed in participants in the confirmed deficient cohort with available serum creatinine levels.
Estimated Glomerular Filtration Rate (eGFR)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ml/min/1.73m2
Number Analyzed 535 participants 539 participants 1074 participants
60  (39.3) 60.9  (36.9) 60.5  (38.1)
[1]
Measure Description: The estimated glomerular filtration rate was calculated based on the following variables: race, sex, and serum creatinine using the formula: CFR = 166 x (Scr/0.7) -0.329 x (0.993) Age.
[2]
Measure Analysis Population Description: This variable was analyzed in participants in the confirmed deficient cohort and calculated based on available data.
1.Primary Outcome
Title All-cause, All-location Mortality to Day 90
Hide Description Vital status of the patient at day 90 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, review of obituaries, or information from the Centers for Disease Control and Prevention's National Death Index (NDI).
Time Frame 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis included subjects who had confirmed vitamin D deficiency by LC/MS/MS testing.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 531 528
Measure Type: Count of Participants
Unit of Measure: Participants
125
  23.5%
109
  20.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.26
Comments [Not Specified]
Method Generalized linear model
Comments [Not Specified]
2.Secondary Outcome
Title All-cause, All Location Mortality to Day 28
Hide Description This variable was calculated in participants who were reported alive at day 28. Vital status of the patient at day 28 was determined using any of the following methods: medical record review, phone calls to patient, proxy or healthcare facility, or review of obituaries.
Time Frame Up to 28 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 531 528
Measure Type: Number
Unit of Measure: participants
92 69
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-0.1 to 8.6
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Hospital Mortality to Day 90
Hide Description Analysis of the number of participants who died prior to hospital discharge up to study day 90.
Time Frame Up to 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Participant count is based on available data.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 538 539
Measure Type: Number
Unit of Measure: participants
92 72
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
-0.5 to 8.0
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Alive and Home (Prior Level of Care) at Day 90
Hide Description This endpoint is the count of participants who have survived and are present at home, defined as pre-hospitalization level of care, at day 90.
Time Frame 90 days post randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 528 526
Measure Type: Count of Participants
Unit of Measure: Participants
348
  65.9%
345
  65.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-5.4 to 6.0
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Hospital Length of Stay to Day 90
Hide Description Number of days from enrollment to the day of study hospital discharge up to day 90. Only calculated for patients that survived through day 90.
Time Frame 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 406 418
Mean (Standard Deviation)
Unit of Measure: days
9.1  (9.2) 10.4  (11.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-2.7 to 0.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Healthcare Facility Length of Stay to Day 90
Hide Description Healthcare facility length of stay is the time spent in another hospital or healthcare facility (e.g. long-term acute care [LTAC] hospitals or acute rehabilitation/skilled nursing facility), for the subgroup of participants that were discharged to another healthcare facility after the initial hospitalization. This measure is defined as the number of days from initial hospital discharge to the first facility discharge to home (pre-hospitalization level of care) up to day 90. Healthcare facility LOS is zero for patients discharged to home (pre-hospitalization level of care) from the study hospital. This endpoint will be analyzed only in survivors using SACE methods because healthcare facility length of stay in those who die during the follow-up period is non-informative for this endpoint.
Time Frame 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
This outcome was analyzed only in survivors using SACE methods because healthcare facility length of stay in those who die during the follow-up period is non-informative for this endpoint.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 402 416
Mean (Standard Deviation)
Unit of Measure: days
6.0  (17.5) 8.1  (20.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.2
Confidence Interval (2-Sided) 95%
-4.8 to 0.4
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Ventilator-free Days (VFDs) to Day 28
Hide Description In participants who survive 28 days, ventilator free days (VFDs) is defined as 28 minus duration of ventilation. Duration of ventilation is counted from the first study day of assisted breathing through the last day of assisted breathing provided the last day is prior to day 28. Or it is counted from the first study day of assisted breathing through day 28. For participants discharged with assisted ventilation prior to day 28, a phone call will be required to assess ventilator status at day 28. Participants discharged prior to day 28 (but not to home) on unassisted breathing will be assumed to remain on unassisted breathing through day 28. Isolated periods of ventilation briefer than 24 hours for surgical procedures and ventilation solely for sleep disordered breathing do not count towards duration of ventilation. In participants who never require assisted breathing, duration of ventilation is zero. Participants who do not survive 28 days will be assigned zero VFD.
Time Frame 28 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Excludes subjects who never required assisted breathing or who did not survive 28 days (considered zero vent free days).
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 523 534
Mean (Standard Deviation)
Unit of Measure: days
21.3  (11.3) 22.1  (10.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.1 to 0.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Health-related Quality of Life by EuroQol (EQ-5D-5L)
Hide Description Changes in Quality of life score by EuroQol from baseline to day 90. Change was calculated as the value at day 90 minus the value at baseline. The EuroQol score is based on 5 dimensions of perceived problems: Mobility, Self-Care, Anxiety/Depression, Pain/discomfort, and Usual Activities. Problems with each area are assigned a level from 1-5 with level 1 being no problem and level 5 indicating extreme problems. A unique health state score is defined by combining 1 level from each of the 5 dimensions. Responses can be used to calculate a health utility score55 associated with the given health state that ranges from -0.11 to 1.00 (higher scores are better; 1.00 is perfect health).
Time Frame baseline to study day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects alive and able to be contacted at study day 90 and who had a baseline EQ-5D-5L assessment were analyzed.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 340 346
Mean (Standard Deviation)
Unit of Measure: score on a scale
0.0  (0.2) -0.0  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 0.1
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of Participants Who Developed (New) ARDS to Day 7
Hide Description Presence of ARDS determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio (i.e., imputed P/F ratio) and chest x-ray confirmation. PaO2 = partial pressure of arterial oxygen; FiO2 = percentage of inspired oxygen; SpO2 = peripheral capillary oxygen saturation, an estimate of the amount of oxygen in the blood. For participants with P/F <300 or imputed P/F <300, FiO2 ≥40%, and PEEP ≥5 cm H2O, we determined if hypoxemia was valid, acute, and not fully explained by congestive heart failure (CHF) or fluid overload. PEEP = positive end expiatory pressure.
Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 411 412
Measure Type: Count of Participants
Unit of Measure: Participants
20
   4.9%
17
   4.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-2.1 to 3.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Severity of Acute Respiratory Distress Syndrome (ARDS)
Hide Description Severity of ARDS is determined using the PaO2/FiO2 ratio or SpO2/FiO2 ratio and confirmation of ARDS through chest x-ray reviews. The breakout of mild to severe was categorized as P/F or imputed P/F ratio of 201-300 (mild), 100-200 (moderate), or less than 100 (severe). This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7.
Time Frame 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Those subjects that developed new ARDS after randomization were analyzed for severity.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 20 17
Measure Type: Count of Participants
Unit of Measure: Participants
Mild
6
  30.0%
4
  23.5%
Moderate
9
  45.0%
12
  70.6%
Severe
5
  25.0%
1
   5.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Mild ARDS
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-22.0 to 34.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Moderate ARDS
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -25.6
Confidence Interval (2-Sided) 95%
-56.3 to 5.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Severe ARDS
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 19.1
Confidence Interval (2-Sided) 95%
-2.9 to 41.1
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Worst Acute Kidney Injury (AKI)
Hide Description This physiologic outcome is one of three key organ systems (respiratory, renal, and cardiovascular) used to assess change in organ failure severity from randomization up to study day 7. Worst AKI was determined by using highest daily creatinine values or new use of dialysis/ renal replacement therapy (chronic dialysis participants were excluded). Mild: On-study creatinine levels 1.5 times greater than baseline value or 0.3 mg/dL over the prehospital value. Moderate: On-study creatinine levels 2 times greater than the baseline pre-hospital value. Severe: On-study creatinine creatinine levels are 3 times greater than baseline prehospital value, or the on-study creatinine level is over 4 mg/dL with an acute (1 day) 0.5 mg/dL rise, or participant is on new renal replacement therapy.
Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 484 495
Measure Type: Count of Participants
Unit of Measure: Participants
None
285
  58.9%
297
  60.0%
Mild
70
  14.5%
77
  15.6%
Moderate
48
   9.9%
52
  10.5%
Severe
81
  16.7%
69
  13.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments No AKI
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-7.3 to 5.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Mild AKI
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-5.6 to 3.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Moderate AKI
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-4.4 to 3.2
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments Severe AKI
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-1.7 to 7.3
Estimation Comments [Not Specified]
12.Secondary Outcome
Title New Renal Replacement Therapy (RRT)
Hide Description Participants who were on chronic dialysis at baseline were excluded from the analysis. Participants who started renal replacement therapy on a study day after day 0 and inclusive of day 7 were considered as having new renal replacement therapy. Those who have never started renal replacement therapy over days 0-7 were considered as not having new renal replacement therapy.
Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 489 500
Measure Type: Count of Participants
Unit of Measure: Participants
20
   4.1%
18
   3.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-1.9 to 2.9
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Highest Creatinine Levels
Hide Description The highest recorded creatinine values is taken from available levels reported across the 7 study days for each patient.
Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 518 528
Mean (Standard Error)
Unit of Measure: mg/dL
2.2  (0.1) 2.1  (0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.2 to 0.1
Estimation Comments [Not Specified]
14.Secondary Outcome
Title New Vasopressor Use to Day 7
Hide Description The number of subjects in each arm that are started on a vasopressor after randomization up to study day 7.
Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
need info on this
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 357 360
Measure Type: Count of Participants
Unit of Measure: Participants
43
  12.0%
42
  11.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-4.4 to 5.1
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Highest Cardiovascular SOFA (Sepsis Related Organ Failure Assessment) Score
Hide Description

Cardiovascular score of the Organ SOFA score was used:

Score = 0: MAP* >= 70 mmHg and No Drug;

Score = 1: MAP < 70 mmHg and No Drug;

Score = 2: (Any MAP) ( dopamine<=5 OR any dobutamine ) AND no other drugs (include neosynephrine vasopressin);

Score = 3: (Any MAP) 5 < dopamine <= 15 OR epinephrine <= 0.1 OR norepinephrine <= 0.1 OR neosynephrine <=0.22 OR any dose vasopressin;

Score = 4: (Any MAP) dopamine > 15 OR epinephrine > 0.1 OR norepinephrine > 0.1 OR neosynephrine > 0.22

* MAP = mean arterial pressure

Time Frame Up to 7 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 523 534
Mean (Standard Error)
Unit of Measure: score on a scale
1.4  (0.1) 1.3  (0.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.3 to 0.0
Estimation Comments [Not Specified]
16.Secondary Outcome
Title 25OHD Levels at Day 3
Hide Description Baseline levels will be measured using LC/MS/MS methods (all randomized participants) and at day 3 (the first 300 randomized participants only).
Time Frame 3 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 145 133
Mean (Standard Deviation)
Unit of Measure: ng/mL
46.9  (23.2) 11.4  (5.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 35.5
Confidence Interval (2-Sided) 95%
31.5 to 39.6
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Highest Total Calcium to Day 14
Hide Description Clinically available serum or ionized Ca levels were obtained through day 14 for all randomized patients. This time frame was selected to align with the 25OHD half life of two weeks.
Time Frame 14 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with a clinically available total calcium level up to study day 14
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 507 513
Mean (Standard Deviation)
Unit of Measure: mg/dL
8.9  (0.8) 8.8  (0.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
18.Secondary Outcome
Title Highest Ionized Calcium to Day 14
Hide Description Clinically available serum or ionized calcium levels through day 14 were collected for all randomized participants. This time frame was selected to align with the 25OHD half life of two weeks.
Time Frame up to 14 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects with a clinically available ionized calcium level up to study day 14
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 153 177
Mean (Standard Deviation)
Unit of Measure: mg/dL
4.7  (0.8) 4.6  (0.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.67
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
19.Secondary Outcome
Title Hypercalcemia to Day 14
Hide Description As the half-life of 25OHD is approximately 2 weeks, clinically available serum or ionized calcium levels through study day 14 were collected. The number of participants with hypercalcemia was reported.
Time Frame up to 14 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 513 523
Measure Type: Count of Participants
Unit of Measure: Participants
14
   2.7%
11
   2.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.51
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
20.Secondary Outcome
Title Kidney Stones to Day 90
Hide Description Incident of kidney stones determined by chart review at the end of hospitalization and by self-report at day 90 phone call in those discharged from the hospital prior to day 90.
Time Frame 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects discharged from the hospital prior to study day 90.
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 507 507
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
3
   0.6%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.25
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
21.Secondary Outcome
Title Fall-related Fractures to Day 90
Hide Description Incident of fall-related fractures will be determined by chart review at the end of hospitalization and by self-report at day 90 phone call for those discharged from the hospital prior to day 90. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures. Because of this uncertainty and limited data in hospitalized patients, we assessed for incident of fall-related fractures.
Time Frame 90 days after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 507 507
Measure Type: Count of Participants
Unit of Measure: Participants
4
   0.8%
2
   0.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.69
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
22.Secondary Outcome
Title Falls to Day 90
Hide Description We assessed for incidence of falls by chart review at the end of hospitalization and by self-report at the 90 day phone call. Most data suggest that high dose vitamin D in healthy outpatients may improve muscle function, balance, and bone mineral density, and thus decrease fall-related fractures, but other data suggest that high dose vitamin D supplementation may actually increase the incidence of falls/fractures.
Time Frame 90 days post randomization
Hide Outcome Measure Data
Hide Analysis Population Description
need to give info
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description:

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

Overall Number of Participants Analyzed 507 507
Measure Type: Count of Participants
Unit of Measure: Participants
36
   7.1%
27
   5.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection High Dose Vitamin D Formulation, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.24
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Time Frame Subjects were assessed for adverse events from enrollment (signing of the informed consent) through study day 14 or hospital discharge, whichever occurs first. Investigators will determine if the event is serious or related to the study drug. The rationale for this time window is the 2 week half-life of 25OHD, which helps to define the period at risk from vitamin D.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title High Dose Vitamin D Formulation Placebo
Hide Arm/Group Description

A single dose of 540,000 IU vitamin D3 will be administered within 2 hours of randomization time.

Vitamin D3: 540,000 IU vitamin D3

A single, liquid enteral placebo dose administered either orally or via naso/orogastric tube will be administered within 2 hours of randomization time.

Placebo: A single, liquid enteral dose administered either orally or via naso/orogastric tube

All-Cause Mortality
High Dose Vitamin D Formulation Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   159/681 (23.35%)      137/656 (20.88%)    
Hide Serious Adverse Events
High Dose Vitamin D Formulation Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/690 (2.03%)      18/668 (2.69%)    
Blood and lymphatic system disorders     
Heparin Induced Thrombocytopenia and Thrombosis  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Cardiac disorders     
Cardiac Arrest  1  1/690 (0.14%)  1 1/668 (0.15%)  1
Cardiomyopathy  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Cardiopulmonary Arrest  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Fluid Overload  1  0/690 (0.00%)  0 1/668 (0.15%)  1
PEA  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Pulmonary Edema  1  0/690 (0.00%)  0 1/668 (0.15%)  2
Ventricular Tachycardia  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Gastrointestinal disorders     
Hemorrhage Jejunum  1  1/690 (0.14%)  1 0/668 (0.00%)  0
General disorders     
Death  1  2/690 (0.29%)  2 0/668 (0.00%)  0
ED Visit  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Readmission  1  2/690 (0.29%)  2 0/668 (0.00%)  0
Readmission to MICU  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Weakness Left Sided  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Infections and infestations     
C Difficile Toxin  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Colitis Pseudomembranous  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Injury, poisoning and procedural complications     
Fall  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Hearing Impaired  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Nervous system disorders     
Altered Mental Status  1  1/690 (0.14%)  1 1/668 (0.15%)  1
Blindness  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Cerebral Infarction  1  1/690 (0.14%)  1 0/668 (0.00%)  0
CVA  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Seizure  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Renal and urinary disorders     
Renal Failure Acute  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Ureteral Calculus  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Ureteral Obstruction from Renal Stone  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Breathing Kussmaul Type  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Lung Disease Obstructive  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Pneumothorax  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Pulmonary Infarction  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Shortness of Breath  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Vascular disorders     
Hemorrahge Retroperitoneal  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Hypertension  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Hypotension, Unresponsive  1  1/690 (0.14%)  1 0/668 (0.00%)  0
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
High Dose Vitamin D Formulation Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/690 (1.45%)      6/668 (0.90%)    
Blood and lymphatic system disorders     
Anemia Microcytic  1  1/690 (0.14%)  2 0/668 (0.00%)  0
Cardiac disorders     
Atrial Fibrillation  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Ventricular Tachycardia  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Endocrine disorders     
Hypercalcemia  1  2/690 (0.29%)  2 0/668 (0.00%)  0
Gastrointestinal disorders     
Emesis  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Nausea  1  2/690 (0.29%)  2 1/668 (0.15%)  1
Nausea and Vomitting  1  1/690 (0.14%)  1 0/668 (0.00%)  0
General disorders     
Confidentiality  1  1/690 (0.14%)  1 1/668 (0.15%)  1
Fatigue  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Infections and infestations     
Pneumonia  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Investigations     
Platelets Decreased  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Renal and urinary disorders     
Discoloration Urine  1  0/690 (0.00%)  0 1/668 (0.15%)  1
Renal Failure Acute  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Aspiration Pneumonia  1  1/690 (0.14%)  1 0/668 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash  1  1/690 (0.14%)  1 0/668 (0.00%)  0
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
The Data and Safety Monitoring Board recommended that the trial be stopped at the first interim analysis when the primary outcome of the study crossed a protocol specified futility boundary. This adaptive design element resulted in a completed study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Nancy Ringwood, CCC Project Manager
Organization: Massachusetts General Hospital
Phone: 617-724-9836
EMail: nringwood@mgh.harvard.edu
Layout table for additonal information
Responsible Party: Boyd Taylor Thompson, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03096314    
Other Study ID Numbers: PETAL02VIOLET
1U01HL123009 ( U.S. NIH Grant/Contract )
First Submitted: February 21, 2017
First Posted: March 30, 2017
Results First Submitted: December 10, 2019
Results First Posted: January 27, 2020
Last Update Posted: January 27, 2020