Roland Buhl1, Sheldon Magder2, Ulrich Bothner3, Kay Tetzlaff4, Florian Voß3, Lazaro Loaiza3, Claus F Vogelmeier5, Lorcan McGarvey6. 1. Pulmonary Department, Mainz University Hospital, Mainz, Germany. Electronic address: r.buhl@3-med.klinik.uni-mainz.de. 2. Royal Victoria Hospital, Montreal, Quebec, Canada. 3. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. 4. Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; Department of Sports Medicine, Medical Clinic V, University of Tübingen, Tübingen, Germany. 5. Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-University Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany. 6. Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
Abstract
BACKGROUND: Long-term safety, particularly cardiovascular safety, is of special interest in maintenance treatment of chronic obstructive pulmonary disease (COPD) with long-acting β2-agonists and long-acting muscarinic antagonists, given potential cardiovascular effects. METHODS: Two 52-week Phase III trials (TONADO®) investigated tiotropium/olodaterol (5/5 and 2.5/5 μg) versus tiotropium 2.5, 5 μg and olodaterol 5 μg. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs), electrocardiogram and laboratory data were pooled. All serious AE (SAE) reports were reviewed by an independent Adjudication Committee, which assessed whether deaths, hospitalisations or intubations were respiratory, cardiovascular, cerebrovascular or other disease related. Subgroup analyses investigated cardiovascular safety including major cardiac events in patients with cardiovascular co-morbidities. RESULTS: This analysis comprised 3100 patients with moderate to very severe COPD, treated for ≤1 year, including 784 patients with cardiovascular co-morbidities. AEs were balanced across treatments in the total population as well as in patient subgroups with pre-existing cardiovascular co-morbidities. The incidence and nature of events were consistent with the disease under study and a 1-year trial duration. 494/3100 patients contributed to an adjudicated analysis of SAEs: 260 had respiratory-related, 53 had cardiovascular-related and 16 had cerebrovascular-related SAEs. Incidences of these SAEs were comparable between treatments. There was no evidence of any increased risk for the combination compared to the monotherapy groups. CONCLUSIONS: These data provide confidence for clinicians that tiotropium/olodaterol 5/5 μg can be safely administered once-daily to patients with moderate to very severe COPD long-term, including those with significant cardiovascular co-morbidity. TRIAL REGISTRY: ClinicalTrials.gov, Nos.: NCT01431274, NCT01431287.
RCT Entities:
BACKGROUND: Long-term safety, particularly cardiovascular safety, is of special interest in maintenance treatment of chronic obstructive pulmonary disease (COPD) with long-acting β2-agonists and long-acting muscarinic antagonists, given potential cardiovascular effects. METHODS: Two 52-week Phase III trials (TONADO®) investigated tiotropium/olodaterol (5/5 and 2.5/5 μg) versus tiotropium 2.5, 5 μg and olodaterol 5 μg. In a pre-specified safety analysis, investigator-reported treatment-emergent adverse events (AEs), electrocardiogram and laboratory data were pooled. All serious AE (SAE) reports were reviewed by an independent Adjudication Committee, which assessed whether deaths, hospitalisations or intubations were respiratory, cardiovascular, cerebrovascular or other disease related. Subgroup analyses investigated cardiovascular safety including major cardiac events in patients with cardiovascular co-morbidities. RESULTS: This analysis comprised 3100 patients with moderate to very severe COPD, treated for ≤1 year, including 784 patients with cardiovascular co-morbidities. AEs were balanced across treatments in the total population as well as in patient subgroups with pre-existing cardiovascular co-morbidities. The incidence and nature of events were consistent with the disease under study and a 1-year trial duration. 494/3100 patients contributed to an adjudicated analysis of SAEs: 260 had respiratory-related, 53 had cardiovascular-related and 16 had cerebrovascular-related SAEs. Incidences of these SAEs were comparable between treatments. There was no evidence of any increased risk for the combination compared to the monotherapy groups. CONCLUSIONS: These data provide confidence for clinicians that tiotropium/olodaterol 5/5 μg can be safely administered once-daily to patients with moderate to very severe COPD long-term, including those with significant cardiovascular co-morbidity. TRIAL REGISTRY: ClinicalTrials.gov, Nos.: NCT01431274, NCT01431287.
Authors: Lianne Parkin; Sheila Williams; David Barson; Katrina Sharples; Simon Horsburgh; Rod Jackson; Jack Dummer Journal: BMJ Open Respir Res Date: 2021-01
Authors: Gary T Ferguson; François Maltais; Jill Karpel; Ulrich Bothner; Isabel Kloer; Matthias Trampisch; Roland Buhl Journal: NPJ Prim Care Respir Med Date: 2020-12-04 Impact factor: 2.871
Authors: Stefan Andreas; Lorcan McGarvey; Ulrich Bothner; Matthias Trampisch; Alberto de la Hoz; Matjaz Fležar; Roland Buhl; Peter Alter Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-08-10
Authors: Stefan Andreas; Ulrich Bothner; Alberto de la Hoz; Isabel Kloer; Matthias Trampisch; Peter Alter Journal: Int J Chron Obstruct Pulmon Dis Date: 2020-08-10