Trial Outcomes & Findings for Low vs. Moderate to High Dose Vitamin D for Prevention of COVID-19 (NCT NCT04868903)
NCT ID: NCT04868903
Last Updated: 2025-12-10
Results Overview
For this outcome, hazard models will be employed to assess the effect of each vitamin D dosing strategy on the outcome. We will first develop hazard ratios for between-group analyses on the primary outcome using log-rank tests, and then develop Cox proportional hazard models to model the hazard function on a set of covariates including but not limited to, moderate or high vitamin D dose, baseline vitamin D levels, age, gender, race, ethnicity, sun exposure, sleep habits, exposure of cohabitants, job type, and study site. We will also control for randomization date to adjust the underlying hazard function for COVID-19 prevalence over time. While our primary analysis will pool subjects randomized to either the moderate or high dose and compare them to low dose subjects, we will also perform secondary analyses comparing low to moderate and low to high and additional analyses that use post randomization vitamin D levels as time varying covariates.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
1475 participants
Primary outcome timeframe
Up to 9-months
Results posted on
2025-12-10
Participant Flow
Participants recruited at the UChicago Medicine main hospital on Chicago's South Side or south suburban Ingalls Hospital and Rush University Medical Center on Chicago's West Side. We planned to enroll 2,000 persons to achieve 80% power to identify a 25% reduction in incidence (P\<0.05). Recruitment began Nov. 23, 2020 and concluded Mar. 30, 2023. Pharmacy staff assigned participants to treatment using a blocked randomization list. 1475 persons consented and 923 randomized and received vitamin D.
Of 1475 consenting participants, only 923 were randomized and received vitamin D after exclusions due to not completing baseline surveys or labs or baseline lab values that identified the participant did not meet inclusion criteria.
Participant milestones
| Measure |
Low Dose Vitamin D (moderate versus low branch)
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
300
|
299
|
162
|
162
|
|
Overall Study
COMPLETED
|
268
|
250
|
143
|
146
|
|
Overall Study
NOT COMPLETED
|
32
|
49
|
19
|
16
|
Reasons for withdrawal
| Measure |
Low Dose Vitamin D (moderate versus low branch)
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
29
|
44
|
17
|
12
|
|
Overall Study
Hyperparathyroidism
|
3
|
5
|
2
|
3
|
Baseline Characteristics
One high dose participant was missing a baseline vitamin D level.
Baseline characteristics by cohort
| Measure |
Low Dose Vitamin D (Moderate Versus Low Branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (High Versus Low Branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Total
n=923 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
46.2 years
STANDARD_DEVIATION 15.4 • n=300 Participants
|
48.4 years
STANDARD_DEVIATION 14.6 • n=299 Participants
|
47.9 years
STANDARD_DEVIATION 14.8 • n=162 Participants
|
45.0 years
STANDARD_DEVIATION 13.3 • n=162 Participants
|
47.0 years
STANDARD_DEVIATION 14.7 • n=923 Participants
|
|
Sex: Female, Male
Female
|
230 Participants
n=300 Participants
|
226 Participants
n=299 Participants
|
115 Participants
n=162 Participants
|
119 Participants
n=162 Participants
|
690 Participants
n=923 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=300 Participants
|
73 Participants
n=299 Participants
|
47 Participants
n=162 Participants
|
43 Participants
n=162 Participants
|
233 Participants
n=923 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=300 Participants
|
1 Participants
n=299 Participants
|
0 Participants
n=162 Participants
|
0 Participants
n=162 Participants
|
2 Participants
n=923 Participants
|
|
Race (NIH/OMB)
Asian
|
34 Participants
n=300 Participants
|
29 Participants
n=299 Participants
|
7 Participants
n=162 Participants
|
11 Participants
n=162 Participants
|
81 Participants
n=923 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=300 Participants
|
1 Participants
n=299 Participants
|
0 Participants
n=162 Participants
|
0 Participants
n=162 Participants
|
1 Participants
n=923 Participants
|
|
Race (NIH/OMB)
Black or African American
|
37 Participants
n=300 Participants
|
43 Participants
n=299 Participants
|
27 Participants
n=162 Participants
|
19 Participants
n=162 Participants
|
126 Participants
n=923 Participants
|
|
Race (NIH/OMB)
White
|
202 Participants
n=300 Participants
|
205 Participants
n=299 Participants
|
108 Participants
n=162 Participants
|
114 Participants
n=162 Participants
|
629 Participants
n=923 Participants
|
|
Race (NIH/OMB)
More than one race
|
8 Participants
n=300 Participants
|
4 Participants
n=299 Participants
|
2 Participants
n=162 Participants
|
5 Participants
n=162 Participants
|
19 Participants
n=923 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
18 Participants
n=300 Participants
|
16 Participants
n=299 Participants
|
18 Participants
n=162 Participants
|
13 Participants
n=162 Participants
|
65 Participants
n=923 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
28 Participants
n=300 Participants
|
27 Participants
n=299 Participants
|
26 Participants
n=162 Participants
|
16 Participants
n=162 Participants
|
97 Participants
n=923 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
268 Participants
n=300 Participants
|
269 Participants
n=299 Participants
|
134 Participants
n=162 Participants
|
143 Participants
n=162 Participants
|
814 Participants
n=923 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=300 Participants
|
3 Participants
n=299 Participants
|
2 Participants
n=162 Participants
|
3 Participants
n=162 Participants
|
12 Participants
n=923 Participants
|
|
Baseline Vitamin D Level
|
36.8 ng/ml
STANDARD_DEVIATION 16.0 • n=300 Participants • One high dose participant was missing a baseline vitamin D level.
|
36.9 ng/ml
STANDARD_DEVIATION 15.4 • n=299 Participants • One high dose participant was missing a baseline vitamin D level.
|
33.4 ng/ml
STANDARD_DEVIATION 17.2 • n=162 Participants • One high dose participant was missing a baseline vitamin D level.
|
34.7 ng/ml
STANDARD_DEVIATION 17.8 • n=161 Participants • One high dose participant was missing a baseline vitamin D level.
|
35.9 ng/ml
STANDARD_DEVIATION 16.4 • n=922 Participants • One high dose participant was missing a baseline vitamin D level.
|
|
Average Sun Exposure
30 min/day or less
|
212 Participants
n=300 Participants
|
219 Participants
n=299 Participants
|
132 Participants
n=162 Participants
|
124 Participants
n=162 Participants
|
687 Participants
n=923 Participants
|
|
Average Sun Exposure
More than 30 min/day
|
64 Participants
n=300 Participants
|
53 Participants
n=299 Participants
|
25 Participants
n=162 Participants
|
28 Participants
n=162 Participants
|
170 Participants
n=923 Participants
|
|
Average Sun Exposure
Missing/not answered
|
24 Participants
n=300 Participants
|
27 Participants
n=299 Participants
|
5 Participants
n=162 Participants
|
10 Participants
n=162 Participants
|
66 Participants
n=923 Participants
|
|
Insomnia Severity Index
No or Subthreshold
|
259 Participants
n=300 Participants
|
263 Participants
n=299 Participants
|
147 Participants
n=162 Participants
|
141 Participants
n=162 Participants
|
810 Participants
n=923 Participants
|
|
Insomnia Severity Index
Moderate or Severe
|
13 Participants
n=300 Participants
|
6 Participants
n=299 Participants
|
10 Participants
n=162 Participants
|
11 Participants
n=162 Participants
|
40 Participants
n=923 Participants
|
|
Insomnia Severity Index
Missing/not answered
|
28 Participants
n=300 Participants
|
30 Participants
n=299 Participants
|
5 Participants
n=162 Participants
|
10 Participants
n=162 Participants
|
73 Participants
n=923 Participants
|
|
COVID-19 Exposure Outside Work
No
|
222 Participants
n=300 Participants
|
218 Participants
n=299 Participants
|
128 Participants
n=162 Participants
|
128 Participants
n=162 Participants
|
696 Participants
n=923 Participants
|
|
COVID-19 Exposure Outside Work
Yes
|
48 Participants
n=300 Participants
|
55 Participants
n=299 Participants
|
27 Participants
n=162 Participants
|
23 Participants
n=162 Participants
|
153 Participants
n=923 Participants
|
|
COVID-19 Exposure Outside Work
Missing/not answered
|
30 Participants
n=300 Participants
|
26 Participants
n=299 Participants
|
7 Participants
n=162 Participants
|
11 Participants
n=162 Participants
|
74 Participants
n=923 Participants
|
|
Employment
No
|
51 Participants
n=300 Participants
|
53 Participants
n=299 Participants
|
27 Participants
n=162 Participants
|
29 Participants
n=162 Participants
|
160 Participants
n=923 Participants
|
|
Employment
Yes
|
246 Participants
n=300 Participants
|
244 Participants
n=299 Participants
|
134 Participants
n=162 Participants
|
131 Participants
n=162 Participants
|
755 Participants
n=923 Participants
|
|
Employment
Missing/not answered
|
3 Participants
n=300 Participants
|
2 Participants
n=299 Participants
|
1 Participants
n=162 Participants
|
2 Participants
n=162 Participants
|
8 Participants
n=923 Participants
|
|
Study Site
UChicago Medicine
|
126 Participants
n=300 Participants
|
115 Participants
n=299 Participants
|
87 Participants
n=162 Participants
|
89 Participants
n=162 Participants
|
417 Participants
n=923 Participants
|
|
Study Site
Rush U Medical Ctr
|
174 Participants
n=300 Participants
|
184 Participants
n=299 Participants
|
75 Participants
n=162 Participants
|
73 Participants
n=162 Participants
|
506 Participants
n=923 Participants
|
|
Randomization Date
Potential Participation Only Before Omicron Arrival
|
48 Participants
n=300 Participants
|
47 Participants
n=299 Participants
|
28 Participants
n=162 Participants
|
29 Participants
n=162 Participants
|
152 Participants
n=923 Participants
|
|
Randomization Date
Potential Participation after Omicron Arrival
|
252 Participants
n=300 Participants
|
252 Participants
n=299 Participants
|
134 Participants
n=162 Participants
|
133 Participants
n=162 Participants
|
771 Participants
n=923 Participants
|
PRIMARY outcome
Timeframe: Up to 9-monthsPopulation: Secondary analysis includes participants seroconverting from negative to positive COV-NAb.
For this outcome, hazard models will be employed to assess the effect of each vitamin D dosing strategy on the outcome. We will first develop hazard ratios for between-group analyses on the primary outcome using log-rank tests, and then develop Cox proportional hazard models to model the hazard function on a set of covariates including but not limited to, moderate or high vitamin D dose, baseline vitamin D levels, age, gender, race, ethnicity, sun exposure, sleep habits, exposure of cohabitants, job type, and study site. We will also control for randomization date to adjust the underlying hazard function for COVID-19 prevalence over time. While our primary analysis will pool subjects randomized to either the moderate or high dose and compare them to low dose subjects, we will also perform secondary analyses comparing low to moderate and low to high and additional analyses that use post randomization vitamin D levels as time varying covariates.
Outcome measures
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D
n=462 Participants
Subjects in these arms will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Pooled Moderate or High Dose Vitamin D
n=461 Participants
Subjects in these arms will be randomized to receive moderate or high dose vitamin D therapy (oral, 4,000 or 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|---|---|
|
SARS-CoV-2 Infection as Measured by Patient Report of Clinically Confirmed COVID-19 (or Viral PCR When Available)
Primary Analysis
|
48 Participants
|
30 Participants
|
20 Participants
|
20 Participants
|
68 Participants
|
50 Participants
|
|
SARS-CoV-2 Infection as Measured by Patient Report of Clinically Confirmed COVID-19 (or Viral PCR When Available)
Secondary Analysis
|
32 Participants
|
17 Participants
|
11 Participants
|
14 Participants
|
43 Participants
|
31 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 9 monthsThis will be measured by a binary indicator of whether the patient is hospitalized after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
Outcome measures
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D
n=462 Participants
Subjects in these arms will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Pooled Moderate or High Dose Vitamin D
n=461 Participants
Subjects in these arms will be randomized to receive moderate or high dose vitamin D therapy (oral, 4,000 or 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|---|---|
|
Hospitalization Following COVID-19
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 9 monthsThis will be measured by a binary indicator of whether the patient is admitted to the ICU after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
Outcome measures
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D
n=462 Participants
Subjects in these arms will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Pooled Moderate or High Dose Vitamin D
n=461 Participants
Subjects in these arms will be randomized to receive moderate or high dose vitamin D therapy (oral, 4,000 or 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|---|---|
|
ICU Stay Following COVID-19
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 9 monthsThis will be measured by a binary indicator of whether the patient receives mechanical ventilation after COVID-19 in the first quarterly survey after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
Outcome measures
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D
n=462 Participants
Subjects in these arms will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Pooled Moderate or High Dose Vitamin D
n=461 Participants
Subjects in these arms will be randomized to receive moderate or high dose vitamin D therapy (oral, 4,000 or 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|---|---|
|
Ventilator Use Following COVID-19
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 9 monthsThis will be measured by a binary indicator of whether the patient dies after COVID-19 in the first quarterly survey up to 9 months after COVID-19 is reported and will be analyzed with a generalized linear model with covariates as in the secondary outcome measure.
Outcome measures
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 Participants
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D
n=462 Participants
Subjects in these arms will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Pooled Moderate or High Dose Vitamin D
n=461 Participants
Subjects in these arms will be randomized to receive moderate or high dose vitamin D therapy (oral, 4,000 or 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|---|---|
|
Death Following COVID-19
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Low Dose Vitamin D (moderate versus low branch)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Moderate Dose Vitamin D
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Low Dose Vitamin D (high versus low branch)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
High Dose Vitamin D
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Dose Vitamin D (moderate versus low branch)
n=300 participants at risk
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
Moderate Dose Vitamin D
n=299 participants at risk
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 4,000 IU/day) for up to 9 continuous months.
|
Low Dose Vitamin D (high versus low branch)
n=162 participants at risk
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 400 IU/day) for up to 9 continuous months.
|
High Dose Vitamin D
n=162 participants at risk
Subjects in this arm will be randomized to receive low dose vitamin D therapy (oral, 10,000 IU/day) for up to 9 continuous months.
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/300 • Up to 9 months after randomization
|
0.00%
0/299 • Up to 9 months after randomization
|
0.00%
0/162 • Up to 9 months after randomization
|
0.62%
1/162 • Up to 9 months after randomization
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place