Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: the VIDA randomized clinical trial.
OBJECTIVE
In asthma and other diseases, vitamin D insufficiency is associated with adverse outcomes. It is not known if supplementing inhaled corticosteroids with oral vitamin D3 improves outcomes in patients with asthma and vitamin D insufficiency.


OBJECTIVE
To evaluate if vitamin D supplementation would improve the clinical efficacy of inhaled corticosteroids in patients with symptomatic asthma and lower vitamin D levels.


METHODS
The VIDA (Vitamin D Add-on Therapy Enhances Corticosteroid Responsiveness in Asthma) randomized, double-blind, parallel, placebo-controlled trial studying adult patients with symptomatic asthma and a serum 25-hydroxyvitamin D level of less than 30 ng/mL was conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by January 2014. After a run-in period that included treatment with an inhaled corticosteroid, 408 patients were randomized.


METHODS
Oral vitamin D3 (100,000 IU once, then 4000 IU/d for 28 weeks; n = 201) or placebo (n = 207) was added to inhaled ciclesonide (320 µg/d). If asthma control was achieved after 12 weeks, ciclesonide was tapered to 160 µg/d for 8 weeks, then to 80 µg/d for 8 weeks if asthma control was maintained.


METHODS
The primary outcome was time to first asthma treatment failure (a composite outcome of decline in lung function and increases in use of β-agonists, systemic corticosteroids, and health care).


RESULTS
Treatment with vitamin D3 did not alter the rate of first treatment failure during 28 weeks (28% [95% CI, 21%-34%] with vitamin D3 vs 29% [95% CI, 23%-35%] with placebo; adjusted hazard ratio, 0.9 [95% CI, 0.6-1.3]). Of 14 prespecified secondary outcomes, 9 were analyzed, including asthma exacerbation; of those 9, the only statistically significant outcome was a small difference in the overall dose of ciclesonide required to maintain asthma control (111.3 µg/d [95% CI, 102.2-120.4 µg/d] in the vitamin D3 group vs 126.2 µg/d [95% CI, 117.2-135.3 µg/d] in the placebo group; difference of 14.9 µg/d [95% CI, 2.1-27.7 µg/d]).


CONCLUSIONS
Vitamin D3 did not reduce the rate of first treatment failure or exacerbation in adults with persistent asthma and vitamin D insufficiency. These findings do not support a strategy of therapeutic vitamin D3 supplementation in patients with symptomatic asthma.


BACKGROUND
clinicaltrials.gov Identifier: NCT01248065.
Washington University School of Medicine, St Louis, Missouri.
Mario
M
Castro
Penn State University, Hershey, Pennsylvania.
Tonya S
TS
King
Penn State University, Hershey, Pennsylvania.
Susan J
SJ
Kunselman
University of California, San Francisco.
Michael D
MD
Cabana
University of Wisconsin, Madison.
Loren
L
Denlinger
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Fernando
F
Holguin
Brigham and Women's Hospital, Boston, Massachusetts.
Shamsah D
SD
Kazani
Wake Forest School of Medicine, Winston-Salem, North Carolina.
Wendy C
WC
Moore
Stroger Hospital of Cook County, Chicago, Illinois.
James
J
Moy
University of Wisconsin, Madison.
Christine A
CA
Sorkness
Northwestern University, Chicago, Illinois.
Pedro
P
Avila
Washington University School of Medicine, St Louis, Missouri.
Leonard B
LB
Bacharier
Wake Forest School of Medicine, Winston-Salem, North Carolina.
Eugene
E
Bleecker
University of California, San Francisco.
Homer A
HA
Boushey
Rainbow Babies and Children's Hospital, Cleveland, Ohio.
James
J
Chmiel
Emory University, Atlanta, Georgia.
Anne M
AM
Fitzpatrick
Allegheny General Hospital, Pittsburgh, Pennsylvania.
Deborah
D
Gentile
Duke University School of Medicine, Durham, North Carolina.
Mandeep
M
Hundal
Brigham and Women's Hospital, Boston, Massachusetts.
Elliot
E
Israel
Duke University School of Medicine, Durham, North Carolina.
Monica
M
Kraft
University of Illinois, Chicago.
Jerry A
JA
Krishnan
North Carolina Clinical Research, Raleigh.
Craig
C
LaForce
University of California, San Francisco.
Stephen C
SC
Lazarus
University of Wisconsin, Madison.
Robert
R
Lemanske
Duke University School of Medicine, Durham, North Carolina.
Njira
N
Lugogo
National Jewish Health, Denver, Colorado.
Richard J
RJ
Martin
Penn State University, Hershey, Pennsylvania.
David T
DT
Mauger
University of Chicago, Chicago, Illinois.
Edward
E
Naureckas
Wake Forest School of Medicine, Winston-Salem, North Carolina.
Stephen P
SP
Peters
Boston Children's Hospital, Boston, Massachusetts.
Wanda
W
Phipatanakul
Duke University School of Medicine, Durham, North Carolina.
Loretta G
LG
Que
Washington University School of Medicine, St Louis, Missouri.
Ajay
A
Sheshadri
Northwestern University, Chicago, Illinois.
Lewis
L
Smith
University of Chicago, Chicago, Illinois.
Julian
J
Solway
Aurora Sinai Medical Center, Milwaukee, Wisconsin.
Lisa
L
Sullivan-Vedder
Washington University School of Medicine, St Louis, Missouri.
Kaharu
K
Sumino
National Jewish Health, Denver, Colorado.
Michael E
ME
Wechsler
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Sally
S
Wenzel
University of Chicago, Chicago, Illinois.
Steven R
SR
White
National Jewish Health, Denver, Colorado20Dr Sutherland is now with sanofi.
E Rand
ER
Sutherland
D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage; D001249:Asthma / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002762:Cholecalciferol / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011282:Pregnenediones / Q000008:administration & dosage*; D017211:Treatment Failure; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy*; D014815:Vitamins / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D011282:Pregnenediones; D014815:Vitamins; D002762:Cholecalciferol; C120481:ciclesonide