Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: The VIDA randomized clinical trial

Mario Castro, Tonya S. King, Susan J. Kunselman, Michael D. Cabana, Loren Denlinger, Fernando Holguin, Shamsah D. Kazani, Wendy C. Moore, James Moy, Christine A. Sorkness, Pedro Avila, Leonard B. Bacharier, Eugene Bleecker, Homer A. Boushey, James Chmiel, Anne M. Fitzpatrick, Deborah Gentile, Mandeep Hundal, Elliot Israel, Monica KraftJerry A. Krishnan, Craig LaForce, Stephen C. Lazarus, Robert Lemanske, Njira Lugogo, Richard J. Martin, David T. Mauger, Edward Naureckas, Stephen P. Peters, Wanda Phipatanakul, Loretta G. Que, Ajay Sheshadri, Lewis Smith, Julian Solway, Lisa Sullivan-Vedder, Kaharu Sumino, Michael E. Wechsler, Sally Wenzel, Steven R. White, E. Rand Sutherland

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Oral vitamin D 3 (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. MAIN OUTCOMES AND MEASURES: The primary outcomewas 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248065.

Original languageEnglish (US)
Pages (from-to)2083-2091
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume311
Issue number20
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Cholecalciferol
Treatment Failure
Vitamin D
Asthma
Randomized Controlled Trials
Adrenal Cortex Hormones
Placebos
National Heart, Lung, and Blood Institute (U.S.)
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels : The VIDA randomized clinical trial. / Castro, Mario; King, Tonya S.; Kunselman, Susan J.; Cabana, Michael D.; Denlinger, Loren; Holguin, Fernando; Kazani, Shamsah D.; Moore, Wendy C.; Moy, James; Sorkness, Christine A.; Avila, Pedro; Bacharier, Leonard B.; Bleecker, Eugene; Boushey, Homer A.; Chmiel, James; Fitzpatrick, Anne M.; Gentile, Deborah; Hundal, Mandeep; Israel, Elliot; Kraft, Monica; Krishnan, Jerry A.; LaForce, Craig; Lazarus, Stephen C.; Lemanske, Robert; Lugogo, Njira; Martin, Richard J.; Mauger, David T.; Naureckas, Edward; Peters, Stephen P.; Phipatanakul, Wanda; Que, Loretta G.; Sheshadri, Ajay; Smith, Lewis; Solway, Julian; Sullivan-Vedder, Lisa; Sumino, Kaharu; Wechsler, Michael E.; Wenzel, Sally; White, Steven R.; Sutherland, E. Rand.

In: JAMA - Journal of the American Medical Association, Vol. 311, No. 20, 01.01.2014, p. 2083-2091.

Research output: Contribution to journalArticle

Castro, M, King, TS, Kunselman, SJ, Cabana, MD, Denlinger, L, Holguin, F, Kazani, SD, Moore, WC, Moy, J, Sorkness, CA, Avila, P, Bacharier, LB, Bleecker, E, Boushey, HA, Chmiel, J, Fitzpatrick, AM, Gentile, D, Hundal, M, Israel, E, Kraft, M, Krishnan, JA, LaForce, C, Lazarus, SC, Lemanske, R, Lugogo, N, Martin, RJ, Mauger, DT, Naureckas, E, Peters, SP, Phipatanakul, W, Que, LG, Sheshadri, A, Smith, L, Solway, J, Sullivan-Vedder, L, Sumino, K, Wechsler, ME, Wenzel, S, White, SR & Sutherland, ER 2014, 'Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: The VIDA randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 311, no. 20, pp. 2083-2091. https://doi.org/10.1001/jama.2014.5052
Castro, Mario ; King, Tonya S. ; Kunselman, Susan J. ; Cabana, Michael D. ; Denlinger, Loren ; Holguin, Fernando ; Kazani, Shamsah D. ; Moore, Wendy C. ; Moy, James ; Sorkness, Christine A. ; Avila, Pedro ; Bacharier, Leonard B. ; Bleecker, Eugene ; Boushey, Homer A. ; Chmiel, James ; Fitzpatrick, Anne M. ; Gentile, Deborah ; Hundal, Mandeep ; Israel, Elliot ; Kraft, Monica ; Krishnan, Jerry A. ; LaForce, Craig ; Lazarus, Stephen C. ; Lemanske, Robert ; Lugogo, Njira ; Martin, Richard J. ; Mauger, David T. ; Naureckas, Edward ; Peters, Stephen P. ; Phipatanakul, Wanda ; Que, Loretta G. ; Sheshadri, Ajay ; Smith, Lewis ; Solway, Julian ; Sullivan-Vedder, Lisa ; Sumino, Kaharu ; Wechsler, Michael E. ; Wenzel, Sally ; White, Steven R. ; Sutherland, E. Rand. / Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels : The VIDA randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2014 ; Vol. 311, No. 20. pp. 2083-2091.
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title = "Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels: The VIDA randomized clinical trial",
abstract = "IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Oral vitamin D 3 (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. MAIN OUTCOMES AND MEASURES: The primary outcomewas 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248065.",
author = "Mario Castro and King, {Tonya S.} and Kunselman, {Susan J.} and Cabana, {Michael D.} and Loren Denlinger and Fernando Holguin and Kazani, {Shamsah D.} and Moore, {Wendy C.} and James Moy and Sorkness, {Christine A.} and Pedro Avila and Bacharier, {Leonard B.} and Eugene Bleecker and Boushey, {Homer A.} and James Chmiel and Fitzpatrick, {Anne M.} and Deborah Gentile and Mandeep Hundal and Elliot Israel and Monica Kraft and Krishnan, {Jerry A.} and Craig LaForce and Lazarus, {Stephen C.} and Robert Lemanske and Njira Lugogo and Martin, {Richard J.} and Mauger, {David T.} and Edward Naureckas and Peters, {Stephen P.} and Wanda Phipatanakul and Que, {Loretta G.} and Ajay Sheshadri and Lewis Smith and Julian Solway and Lisa Sullivan-Vedder and Kaharu Sumino and Wechsler, {Michael E.} and Sally Wenzel and White, {Steven R.} and Sutherland, {E. Rand}",
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TY - JOUR

T1 - Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels

T2 - The VIDA randomized clinical trial

AU - Castro, Mario

AU - King, Tonya S.

AU - Kunselman, Susan J.

AU - Cabana, Michael D.

AU - Denlinger, Loren

AU - Holguin, Fernando

AU - Kazani, Shamsah D.

AU - Moore, Wendy C.

AU - Moy, James

AU - Sorkness, Christine A.

AU - Avila, Pedro

AU - Bacharier, Leonard B.

AU - Bleecker, Eugene

AU - Boushey, Homer A.

AU - Chmiel, James

AU - Fitzpatrick, Anne M.

AU - Gentile, Deborah

AU - Hundal, Mandeep

AU - Israel, Elliot

AU - Kraft, Monica

AU - Krishnan, Jerry A.

AU - LaForce, Craig

AU - Lazarus, Stephen C.

AU - Lemanske, Robert

AU - Lugogo, Njira

AU - Martin, Richard J.

AU - Mauger, David T.

AU - Naureckas, Edward

AU - Peters, Stephen P.

AU - Phipatanakul, Wanda

AU - Que, Loretta G.

AU - Sheshadri, Ajay

AU - Smith, Lewis

AU - Solway, Julian

AU - Sullivan-Vedder, Lisa

AU - Sumino, Kaharu

AU - Wechsler, Michael E.

AU - Wenzel, Sally

AU - White, Steven R.

AU - Sutherland, E. Rand

PY - 2014/1/1

Y1 - 2014/1/1

N2 - IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Oral vitamin D 3 (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. MAIN OUTCOMES AND MEASURES: The primary outcomewas 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248065.

AB - IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Oral vitamin D 3 (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. MAIN OUTCOMES AND MEASURES: The primary outcomewas 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01248065.

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