TRIple in Asthma hiGh strenGth vErsus Ics/Laba hs and tiotRopium (TRIGGER)

This was a phase III, multicentre, randomised, double-blind study, with an open-label arm, active-controlled, 3-arm parallel group study to demonstrate both the superiority of CHF 5993 pMDI 200/6/12.5 μg compared with CHF 1535 pMDI 200/6 μg in terms of change from baseline in pre-dose FEV1 at Week 26 and a reduction of moderate and severe asthma exacerbation rate with CHF 5993 pMDI 200/6/12.5 μg compared to CHF 1535 pMDI 200/6 μg during the entire 52-week treatment period. The study was performed in patients with uncontrolled asthma on high doses of inhaled corticosteroids (ICS) in combination with long acting β2-agonists LABAs). The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and all other requirements of local laws. Patients completed the electronic diary (eDiary)/electronic peak flow meter (ePeakflowmeter) twice daily at home from screening to Week 52, recording asthma symptoms, treatment compliance, rescue intake and peak expiratory flow (PEF). The Asthma Control Questionnaire© (ACQ)-7 was completed at all visits from screening to Week 52. The EuroQuality of Life-5-Dimensional-3-Level (EQ-5D-3L™) questionnaire was completed at all visits from randomisation to Week 52. Health economic information was collected during the study. An independent Data Safety Monitoring Board was established for evaluation of the study and impartial safety assurance for patients. An Adjudication Committee was established to evaluate Major Adverse Cardiovascular Events. Primary objective of the study were: * To demonstrate the superiority of CHF 5993 pMDI 200/6/12.5 μg compared with CHF 1535 pMDI 200/6 μg in terms of change from baseline in pre-dose forced expiratory volume in the 1st second (FEV1) at Week 26; * To demonstrate the reduction of moderate and severe asthma exacerbations rate with CHF 5993 pMDI 200/6/12.5 μg compared with CHF 1535 pMDI 200/6 μg during the entire 52-week treatment period. The secondary endpoints included pooled analyse of 2 pivotal studies; this study (TRIGGER) and study (TRIMARAN). These 2 studies have similar study designs and study population. CHF 1535 pMDI: fixed-dose combination (FDC) of BDP + FF + GB Dose: BDP 200 μg, FF 6 μg, GB 12.5 μg per actuation, 2 inhalations, BID. Total daily dose: BDP 800 μg, FF 24 μg, GB 50 μg. BDP: Beclometasone dipropionate FF: Formoterol fumarate GB: Glycopyrronium bromide