The Effect of the Endothelin-1 Receptor Antagonist, Bosentan, on Patients with Poorly Controlled Asthma: A 17-week, Double-Blind, Placebo-Controlled Crossover Pilot Study

Objective. To determine the effect of bosentan on subjects with poorly controlled asthma. Methods. This was a double-blind, placebo-controlled crossover pilot study. Subjects were poorly controlled on anti-inflammatory and long acting beta-agonist therapy, and had a baseline forced expiratory volume in 1 second (FEV1) percent of predicted of 40-70%. Subjects were randomized to receive either bosentan or placebo at the therapeutic dose of 125 mg twice a day for 4 weeks, and then crossed over to the alternate therapy. The asthma control test, asthma symptom scores, rescue albuterol use, and FEV1 were measured at baseline and during the last week of bosentan and placebo. Acute changes in FEV1 were measured after the initial therapeutic bosentan and placebo dose. Results. Seven of eleven randomized subjects completed the protocol. There was no difference in change in FEV1 after the bosentan phase when compared with placebo (+0.08 +/- 0.31 L and +0.23 +/- 0.26 L p = .34). Changes from baseline values in the asthma control test and asthma symptom scores were also similar in bosentan and placebo phases (+1.71 +/- 3.99 and +4.57 +/- 4.39 p = .16) and (+0.14 +/- 9.3 and -0.29 +/- 5.28 p = .93). Rescue beta-agonist use did not change significantly during the last week of the bosentan phase when compared with placebo phase (-5.86 +/- 0.94 puffs and -5.14 +/- 16.85 puffs p = .94). Additionally, there was no difference in the change in FEV1 4 hours after bosentan 125 mg and placebo (-0.08 L +/- 0.07 vs. +0.04 L +/- 0.20 p = .20). Conclusions. In this pilot study, 4 weeks of bosentan did not improve FEV1, beta-agonist use, asthma symptom score, or asthma control test score in patients with poorly controlled asthma when compared with placebo.