Stephen P. Peters, M.D., Ph.D., Susan J. Kunselman, M.A., Nikolina Icitovic, M.A.S., Wendy C. Moore, M.D., Rodolfo Pascual, M.D., Bill T. Ameredes, Ph.D., Homer A. Boushey, M.D., William J. Calhoun, M.D., Mario Castro, M.D., Reuben M. Cherniack, M.D., Timothy Craig, D.O., Loren Denlinger, M.D., Ph.D., Linda L. Engle, B.S., Emily A. DiMango, M.D., John V. Fahy, M.D., Elliot Israel, M.D., Nizar Jarjour, M.D., Shamsah D. Kazani, M.D., Monica Kraft, M.D., Stephen C. Lazarus, M.D., Robert F. Lemanske, Jr., M.D., Njira Lugogo, M.D., Richard J. Martin, M.D., Deborah A. Meyers, Ph.D., Joe Ramsdell, M.D., Christine A. Sorkness, Pharm.D., E. Rand Sutherland, M.D., Stanley J. Szefler, M.D., Stephen I. Wasserman, M.D., Michael J. Walter, M.D., Michael E. Wechsler, M.D., Vernon M. Chinchilli, Ph.D., and Eugene R. Bleecker, M.D. for the National Heart, Lung, and Blood Institute Asthma Clinical Research Network. N Engl J Med 2010; 363:1715-1726October 28, 2010
Background
Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed.
Methods
In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison).
Results
The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthma-control days, with a difference of 0.079 (P=0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P=0.004); and daily symptom scores, with a difference of −0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P=0.003).
Conclusions
When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.)
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