Early bronchodilator action of glycopyrronium versus tiotropium in moderate-to-severe COPD patients: a cross-over blinded randomized study (Symptoms and Pulmonary function in the moRnING)

摘要

Background: Morning symptoms associated with COPD have a negative impact on patients’ quality of life. Long-acting bronchodilators with rapid onset may relieve patients’ symptoms. In the Symptoms and Pulmonary function in the moRnING study, we prospectively compared the rapid onset bronchodilator profile of glycopyrronium (GLY) and tiotropium (TIO) during the first few hours after dosing in patients with moderate-to-severe COPD. Methods: Patients were randomized (1:1) to receive either once-daily GLY (50 μg) or TIO (18?μg) and corresponding placebos in a cross-over design for 28 days. The primary objective was to demonstrate the superiority of GLY versus TIO in area under the curve from 0 to 4?hours (AUC_0-4h) forced expiratory volume in 1 second (FEV₁) after the first dose. The secondary objective was to compare GLY versus TIO using the patient reported outcomes Morning COPD Symptoms Questionnaire 3 hours post-inhalation. Results: One-hundred and twenty-six patients were randomized (male 70.2%; mean age 65.7?years) and 108 patients completed the study. On Day 1, GLY resulted in significantly higher FEV₁ AUC_0-4h after the first dose versus TIO (treatment difference [Δ], 0.030 L, 95% confidence interval 0.004–0.056, P =0.025). Improvements in morning COPD symptoms from baseline at Days 1 and 28 were similar between GLY and TIO. Post hoc analysis of the FEV₁ AUC_0-4h by time point on Day 1 showed significant improvements in patients receiving GLY versus TIO at 5 minutes (Δ=0.029 L, P=0.015), 15 minutes (Δ=0.033 L, P =0.026), and 1 hour (Δ=0.044 L, P =0.014). Safety results were comparable between both treatments. Conclusion: The SPRING study demonstrates the superiority of GLY versus TIO in terms of superior bronchodilation in the first 4 hours after administration, thus extending the clinical data that support a faster onset of action of GLY versus TIO.