Trial Outcomes & Findings for Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma (NCT NCT01248065)
NCT ID: NCT01248065
Last Updated: 2014-08-13
Results Overview
Treatment failure is a well-defined asthma outcome reflecting overall asthma control that has been used previously in multiple clinical trials. Treatment failure as defined in the current proposal and prior trials is consistent with the American Thoracic Society (ATS)/European Respiratory Society(ERS) definition of a moderate exacerbation - a deterioration in symptoms and/or lung function with increased rescue bronchodilator use that lasts 2 days or more. The percentages of participants experiencing a treatment failure are Kaplan-Meier estimates of failure rate.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
408 participants
Primary outcome timeframe
Twenty-eight week intervention period from randomization until end of trial.
Results posted on
2014-08-13
Participant Flow
Participant milestones
| Measure |
Ciclesonide + Placebo
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Overall Study
STARTED
|
207
|
201
|
|
Overall Study
COMPLETED
|
181
|
179
|
|
Overall Study
NOT COMPLETED
|
26
|
22
|
Reasons for withdrawal
| Measure |
Ciclesonide + Placebo
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
3
|
5
|
|
Overall Study
Withdrawal by Subject
|
14
|
11
|
|
Overall Study
Adverse Event
|
3
|
0
|
|
Overall Study
Third treatment failure event
|
3
|
1
|
|
Overall Study
Other
|
3
|
5
|
Baseline Characteristics
Study of the Effect of Vitamin D as an Add-on Therapy to Corticosteroids in Asthma
Baseline characteristics by cohort
| Measure |
Ciclesonide + Placebo
n=207 Participants
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 Participants
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Total
n=408 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
39.5 years
STANDARD_DEVIATION 12.7 • n=5 Participants
|
39.9 years
STANDARD_DEVIATION 13.1 • n=7 Participants
|
39.7 years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
141 Participants
n=5 Participants
|
137 Participants
n=7 Participants
|
278 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
66 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian/Pacific Islander
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
68 participants
n=5 Participants
|
63 participants
n=7 Participants
|
131 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
111 participants
n=5 Participants
|
105 participants
n=7 Participants
|
216 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
19 participants
n=5 Participants
|
20 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 participants
n=5 Participants
|
6 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Duration of asthma
|
25.0 years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
24.9 years
STANDARD_DEVIATION 13.5 • n=7 Participants
|
25.0 years
STANDARD_DEVIATION 13.2 • n=5 Participants
|
|
Body mass index
|
31.5 kg/m^2
STANDARD_DEVIATION 9.5 • n=5 Participants
|
32.0 kg/m^2
STANDARD_DEVIATION 8.2 • n=7 Participants
|
31.8 kg/m^2
STANDARD_DEVIATION 8.9 • n=5 Participants
|
|
Symptom score (morning)
|
0.41 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.36 • n=5 Participants
|
0.41 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.34 • n=7 Participants
|
0.41 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.35 • n=5 Participants
|
|
Symptom score (afternoon and evening)
|
0.43 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.40 • n=5 Participants
|
0.44 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.35 • n=7 Participants
|
0.43 Avg score of 5 sx: 0=absent to 3=severe
STANDARD_DEVIATION 0.37 • n=5 Participants
|
|
Level of 25-hydroxyvitamin D
|
18.8 ng/mL
n=5 Participants
|
19.9 ng/mL
n=7 Participants
|
19.2 ng/mL
n=5 Participants
|
|
FEV1 before albuterol use (L)
|
2.62 liters
STANDARD_DEVIATION 0.83 • n=5 Participants
|
2.63 liters
STANDARD_DEVIATION 0.78 • n=7 Participants
|
2.63 liters
STANDARD_DEVIATION 0.80 • n=5 Participants
|
|
FEV1 before albuterol use (% predicted)
|
80.5 % predicted
STANDARD_DEVIATION 14.2 • n=5 Participants
|
80.7 % predicted
STANDARD_DEVIATION 13.8 • n=7 Participants
|
80.6 % predicted
STANDARD_DEVIATION 14.0 • n=5 Participants
|
|
Methacholine PC20 (mg/mL)
|
1.85 mg/mL
STANDARD_DEVIATION 1.67 • n=5 Participants
|
2.05 mg/mL
STANDARD_DEVIATION 1.61 • n=7 Participants
|
1.95 mg/mL
STANDARD_DEVIATION 1.65 • n=5 Participants
|
|
Sputum eosinophils (%)
|
0.40 % of eosinophils
n=5 Participants
|
0.30 % of eosinophils
n=7 Participants
|
0.40 % of eosinophils
n=5 Participants
|
PRIMARY outcome
Timeframe: Twenty-eight week intervention period from randomization until end of trial.Treatment failure is a well-defined asthma outcome reflecting overall asthma control that has been used previously in multiple clinical trials. Treatment failure as defined in the current proposal and prior trials is consistent with the American Thoracic Society (ATS)/European Respiratory Society(ERS) definition of a moderate exacerbation - a deterioration in symptoms and/or lung function with increased rescue bronchodilator use that lasts 2 days or more. The percentages of participants experiencing a treatment failure are Kaplan-Meier estimates of failure rate.
Outcome measures
| Measure |
Ciclesonide + Placebo
n=207 Participants
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 Participants
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Treatment Failure
|
29 Percentage of participants
Interval 23.0 to 35.0
|
28 Percentage of participants
Interval 21.0 to 34.0
|
SECONDARY outcome
Timeframe: Change is measured as value at 28 weeks minus baseline value.FEV1 (liters) and methacholine PC20 will be evaluated. Changes are measured as 28 weeks minus baseline.
Outcome measures
| Measure |
Ciclesonide + Placebo
n=207 Participants
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 Participants
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Lung Function Change From Baseline
|
-0.04 Liters
Interval -0.11 to 0.03
|
-0.07 Liters
Interval -0.14 to 0.01
|
SECONDARY outcome
Timeframe: Overall exacerbation rate during 28-week trialOutcome defined as number of exacerbations per person-year.
Outcome measures
| Measure |
Ciclesonide + Placebo
n=207 Participants
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 Participants
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Exacerbations
|
0.40 Exacerbations/person-year
Interval 0.3 to 0.5
|
0.26 Exacerbations/person-year
Interval 0.18 to 0.33
|
Adverse Events
Ciclesonide + Placebo
Serious events: 9 serious events
Other events: 157 other events
Deaths: 0 deaths
Ciclesonide + Vitamin D
Serious events: 6 serious events
Other events: 168 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ciclesonide + Placebo
n=207 participants at risk
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 participants at risk
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Asthma exacerbation
|
1.4%
3/207 • Number of events 6
|
0.50%
1/201 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Initial diagnosis of breast cancer
|
0.48%
1/207 • Number of events 1
|
0.00%
0/201
|
|
Blood and lymphatic system disorders
Severe leg pain
|
0.48%
1/207 • Number of events 1
|
0.00%
0/201
|
|
Gastrointestinal disorders
Sigmoid diverticulitis with abscess
|
0.48%
1/207 • Number of events 2
|
0.00%
0/201
|
|
Gastrointestinal disorders
Gastric volvulus causing gastric outlet obstruction
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
Psychiatric disorders
Major depression disorder
|
0.48%
1/207 • Number of events 1
|
0.00%
0/201
|
|
Psychiatric disorders
Post-traumatic stress disorder
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Allergic reaction/rash
|
0.48%
1/207 • Number of events 1
|
0.00%
0/201
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign fibroid tumor surgery
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
Surgical and medical procedures
Inguinal hernia
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
General disorders
Transient ischemic attack
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
Infections and infestations
Acute sinusitis
|
0.00%
0/207
|
0.50%
1/201 • Number of events 1
|
|
General disorders
Limb edema
|
0.48%
1/207 • Number of events 1
|
0.00%
0/201
|
Other adverse events
| Measure |
Ciclesonide + Placebo
n=207 participants at risk
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
Ciclesonide + Vitamin D
n=201 participants at risk
Vitamin D3: vitamin D (100,000 IU loading dose followed by 4,000 IU/day)
Ciclesonide: Low dose inhaled corticosteroid (80 mcg/puff two puffs twice daily)
|
|---|---|---|
|
Gastrointestinal disorders
Diseases of the digestive system
|
11.1%
23/207 • Number of events 28
|
6.5%
13/201 • Number of events 20
|
|
Renal and urinary disorders
Diseases of the genitourinary system
|
8.7%
18/207 • Number of events 31
|
6.0%
12/201 • Number of events 12
|
|
Musculoskeletal and connective tissue disorders
Diseases of the musculoskeletal system and connective tissue
|
15.0%
31/207 • Number of events 46
|
14.4%
29/201 • Number of events 33
|
|
Nervous system disorders
Diseases of the nervous system and sense organs
|
12.1%
25/207 • Number of events 27
|
11.4%
23/201 • Number of events 30
|
|
Respiratory, thoracic and mediastinal disorders
Diseases of the respiratory system
|
58.9%
122/207 • Number of events 231
|
68.2%
137/201 • Number of events 253
|
|
Infections and infestations
Infectious and parasitic diseases
|
10.6%
22/207 • Number of events 23
|
6.0%
12/201 • Number of events 13
|
|
Injury, poisoning and procedural complications
Injury and poisoning
|
11.1%
23/207 • Number of events 31
|
13.9%
28/201 • Number of events 40
|
|
General disorders
Symptoms, signs, and ill-defined conditions
|
29.0%
60/207 • Number of events 114
|
29.4%
59/201 • Number of events 141
|
Additional Information
Tonya S. King, PhD
Penn State University Dept. of Public Health Sciences
Phone: 717-531-7178
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place