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

Abstract

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 β-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 β-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, β-agonist use, asthma symptom score, or asthma control test score in patients with poorly controlled asthma when compared with placebo.

• asthma
• bosentan
• endothelin-1
• novel therapy
• poorly controlled