Trial Outcomes & Findings for Vitamin D to Prevent Severe Asthma Exacerbations (Vit-D-Kids Asthma) (NCT NCT02687815)

Last Updated: 2021-08-12

Results Overview

A severe asthma exacerbation is defined as an exacerbation that meets either of these criteria: 1) Use of systemic corticosteroids (tablets, suspension, or injection), or an increase from a stable maintenance dose, for at least 3 days OR 2) A hospitalization or ER visit because of asthma, requiring systemic corticosteroids.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

192 participants

Primary outcome timeframe

48 weeks

Results posted on

2021-08-12

Participant Flow

Of 595 participants assessed for eligibility, 192 finished run-in and were randomized.

Participant milestones

Participant milestones
Measure	Vitamin D3 Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Overall Study STARTED	96	96
Overall Study COMPLETED	92	88
Overall Study NOT COMPLETED	4	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Vitamin D3 Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Overall Study Lost to Follow-up	2	4
Overall Study Withdrawal by Subject	2	4

Baseline Characteristics

2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vitamin D3 n=96 Participants Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=96 Participants placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.	Total n=192 Participants Total of all reporting groups
Sex: Female, Male Male	52 Participants n=96 Participants	63 Participants n=96 Participants	115 Participants n=192 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=96 Participants	6 Participants n=96 Participants	13 Participants n=192 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	89 Participants n=96 Participants	90 Participants n=96 Participants	179 Participants n=192 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=96 Participants	0 Participants n=96 Participants	0 Participants n=192 Participants
Race/Ethnicity, Customized Race · White	27 Participants n=96 Participants	32 Participants n=96 Participants	59 Participants n=192 Participants
Age, Continuous	9.9 years STANDARD_DEVIATION 2.5 • n=96 Participants	9.7 years STANDARD_DEVIATION 2.5 • n=96 Participants	9.8 years STANDARD_DEVIATION 2.5 • n=192 Participants
Sex: Female, Male Female	44 Participants n=96 Participants	33 Participants n=96 Participants	77 Participants n=192 Participants
Race/Ethnicity, Customized Race · Black	51 Participants n=96 Participants	49 Participants n=96 Participants	100 Participants n=192 Participants
Race/Ethnicity, Customized Race · Other Race	18 Participants n=96 Participants	15 Participants n=96 Participants	33 Participants n=192 Participants
Region of Enrollment United States	96 participants n=96 Participants	96 participants n=96 Participants	192 participants n=192 Participants
Parental Education High school or less	21 Participants n=94 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	20 Participants n=95 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	41 Participants n=189 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education
Parental Education Some college	22 Participants n=94 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	22 Participants n=95 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	44 Participants n=189 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education
Parental Education Completed college	37 Participants n=94 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	32 Participants n=95 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	69 Participants n=189 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education
Parental Education Postgraduate education	14 Participants n=94 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	21 Participants n=95 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education	35 Participants n=189 Participants • 2 participants from the Vitamin D3 group and 1 participant from the placebo group did not have information on parental education
Household smoke exposure before age 2 years	31 Participants n=94 Participants • 2 participants from Vitamin D3 group and 2 participants from Placebo gorup did not have information on household smoke expousre before age 2 years	32 Participants n=94 Participants • 2 participants from Vitamin D3 group and 2 participants from Placebo gorup did not have information on household smoke expousre before age 2 years	63 Participants n=188 Participants • 2 participants from Vitamin D3 group and 2 participants from Placebo gorup did not have information on household smoke expousre before age 2 years
Current household smoke exposure	25 Participants n=93 Participants • 3 participants from Vitamin D3 group and 3 participants from Placebo group did not have information on household smoke exposure during the study	22 Participants n=93 Participants • 3 participants from Vitamin D3 group and 3 participants from Placebo group did not have information on household smoke exposure during the study	47 Participants n=186 Participants • 3 participants from Vitamin D3 group and 3 participants from Placebo group did not have information on household smoke exposure during the study
Season of enrollment January-March	30 Participants n=96 Participants	25 Participants n=96 Participants	55 Participants n=192 Participants
Season of enrollment April-June	26 Participants n=96 Participants	26 Participants n=96 Participants	52 Participants n=192 Participants
Season of enrollment July-September	22 Participants n=96 Participants	22 Participants n=96 Participants	44 Participants n=192 Participants
Season of enrollment October-December	18 Participants n=96 Participants	23 Participants n=96 Participants	41 Participants n=192 Participants
Asthma Control Test score >19	76 Participants n=96 Participants	73 Participants n=96 Participants	149 Participants n=192 Participants
Body Mass Index z-score	0.9 z-score STANDARD_DEVIATION 1.1 • n=95 Participants • 1 participant in the Vitamin D3 group did not have a valid BMI z-score	0.9 z-score STANDARD_DEVIATION 1.3 • n=96 Participants • 1 participant in the Vitamin D3 group did not have a valid BMI z-score	0.9 z-score STANDARD_DEVIATION 1.2 • n=191 Participants • 1 participant in the Vitamin D3 group did not have a valid BMI z-score
No. of severe exacerbations in the previous year	1 exacerbations n=88 Participants • 8 participants in the Vitamin D3 group and 10 participants in the placebo group did not have such information	1 exacerbations n=86 Participants • 8 participants in the Vitamin D3 group and 10 participants in the placebo group did not have such information	1 exacerbations n=174 Participants • 8 participants in the Vitamin D3 group and 10 participants in the placebo group did not have such information
Vitamin D	22.5 ng/mL STANDARD_DEVIATION 4.6 • n=96 Participants	22.8 ng/mL STANDARD_DEVIATION 4.6 • n=96 Participants	22.6 ng/mL STANDARD_DEVIATION 4.6 • n=192 Participants
FEV1	93.9 % predicted STANDARD_DEVIATION 15.8 • n=96 Participants	90.6 % predicted STANDARD_DEVIATION 17.3 • n=96 Participants	92.2 % predicted STANDARD_DEVIATION 16.6 • n=192 Participants
FEV1/FVC	91.5 % predicted STANDARD_DEVIATION 9.3 • n=96 Participants	89.6 % predicted STANDARD_DEVIATION 10.1 • n=96 Participants	90.6 % predicted STANDARD_DEVIATION 9.7 • n=192 Participants
Asthma Control Test score	22.0 units on a scale STANDARD_DEVIATION 3.2 • n=96 Participants	21.3 units on a scale STANDARD_DEVIATION 3.6 • n=96 Participants	21.7 units on a scale STANDARD_DEVIATION 3.4 • n=192 Participants

PRIMARY outcome

Timeframe: 48 weeks

Population: Intent to treat population across the 48-week study period

Outcome measures

Outcome measures
Measure	Vitamin D3 n=96 Participants Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=96 Participants placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Days to a Severe Asthma Exacerbation	240 Days Standard Deviation 105.8	253 Days Standard Deviation 101.3

SECONDARY outcome

Timeframe: 48 weeks

Population: In Vitamin D3 gorup, 82 with time to viral exacerbation were included in the analysis (14 first exacerbations not tested). In Placebo group, 83 with time to viral exacerbation were included in the analysis (13 first exacerbations not tested)

A severe viral asthma exacerbation is defined as a severe asthma exacerbation \[defined as an exacerbation that meets either of these criteria: 1) Use of systemic corticosteroids (tablets, suspension, or injection), or an increase from a stable maintenance dose, for at least 3 days OR 2) A hospitalization or ER visit because of asthma, requiring systemic corticosteroids\] along with a positive respiratory viral panel from a nasal blow collected within 72 hours of the exacerbation.

Outcome measures

Outcome measures
Measure	Vitamin D3 n=82 Participants Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=83 Participants placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Days to Viral-induced Severe Exacerbation	272 Days Standard Deviation 87.8	281 Days Standard Deviation 83.6

SECONDARY outcome

Timeframe: 24 weeks

Population: In the Vitamin D3 group, 91 subjects with data on reduction in the dose of inhaled corticosteroids (4 withdrew before 24 wk, 1 missed 24-wk visit). In the Placebo group, 91 subjects had data on reduction in the dose of inhaled corticosteroids (4 withdrew before 24 wk, 1 missed 24-wk visit)

In the absence of moderate or severe asthma exacerbations, participants may have their dose of inhaled corticosteroids (ICS) reduced by 50% if the following criteria are met at visit 6 (halfway through the Trial Phase): * Asthma Control Test (ACT) score greater than 19 * Both pre-bronchodilator FEV1 and FEV1/FVC ≥80% of predicted * Use of ≤4 puffs of a rescue inhaler per week * ≤1 day per month with asthma symptoms preventing full participation in usual daily activities * Clinician's judgment regarding adequate asthma control

Outcome measures

Outcome measures
Measure	Vitamin D3 n=91 Participants Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=91 Participants placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Proportion of Participants in Whom Fluticasone Dose Was Halved at Visit 6	28 Participants	29 Participants

SECONDARY outcome

Timeframe: 48 weeks

Population: Intent to treat population across the 48-week study period

The average cumulative dose of inhaled corticosteroids (ICS) during the study period

Outcome measures

Outcome measures
Measure	Vitamin D3 n=96 Participants Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=96 Participants placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Average Cumulative Prescribed Dose of ICS at the End of the Trial	59.6 mg Standard Deviation 22.9	55.2 mg Standard Deviation 14.5

Adverse Events

Vitamin D3

Serious events: 9 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vitamin D3 n=96 participants at risk Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=96 participants at risk placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Respiratory, thoracic and mediastinal disorders Hospitalization for asthma exacerbation	6.2% 6/96 • Number of events 8 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	6.2% 6/96 • Number of events 6 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.
Blood and lymphatic system disorders eosinophilia	1.0% 1/96 • Number of events 1 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	0.00% 0/96 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.
Blood and lymphatic system disorders severe neutropenia	1.0% 1/96 • Number of events 1 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	0.00% 0/96 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.
Respiratory, thoracic and mediastinal disorders Pneumonia/otitis/hives	1.0% 1/96 • Number of events 1 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	0.00% 0/96 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.
Psychiatric disorders Depression	0.00% 0/96 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	2.1% 2/96 • Number of events 3 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.

Other adverse events

Other adverse events
Measure	Vitamin D3 n=96 participants at risk Cholecalciferol (Vitamin D3) 4000 IU oral gel cap daily vitamin D3 4000 IU: The vitamin D3 will be in oral gel cap form and contain 4000 International Units (IU) of cholecalciferol per gel cap.	Placebo n=96 participants at risk placebo formulations will be in gel cap form and identical to the active drug Placebo: The placebo is a gel cap that is indistinguishable from the vitamin D3 gel cap.
Musculoskeletal and connective tissue disorders Fractures	5.2% 5/96 • Number of events 5 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.	4.2% 4/96 • Number of events 4 • 48 weeks A hospitalization for an asthma exacerbation was considered a serious adverse event.

Additional Information

Dr. Juan Celedón

University of Pittsburgh

Phone: (412) 692-8429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place