Chronic obstructive pulmonary disease (COPD) is a chronic, complex disease and is one of the three most frequent causes of death worldwide. Patients with COPD have breath difficulties, cough and sputum, which could lead to reduction in lung function, poorer quality of life and need for hospitalization. COPD cannot be cured, but can be managed by medications, which have been proved to be effective in randomized trials. In this study approved by the authorities within European Medicines Agency (EMA) we will compare two different methods to take the medication to treat COPD: by dry powder inhaler, and by pressurized metered dose inhaler. These two inhalers were assessed to have the same efficacy and safety in COPD patients, although patients may have different personal preferences for the inhalers to use. However, it is unknown if users of different inhalers have different possibilities of developing potential unwanted outcomes in the long-term. Thus, the aim of this study is to compare potential cardiovascular outcomes, like heart diseases, disorders related to the brain blood vessels, or death, in COPD patients using the same medication via different types of inhalers. The five -year study will investigate unwanted outcomes in COPD patients from data aggregated from multiple countries across Europe, including the United Kingdom and the results of the study will be evaluated yearly by authorities within EMA. The study will provide doctors and patients additional evidence on the inhalers regarding vascular safety of COPD patients in their daily life.
The aim of the post-authorisation safety study (PASS), is to assess the incidence rates (IRs) of adverse cardiovascular and cerebrovascular outcomes with the primary outcome defined as ‘major adverse cardiovascular events’ (MACEs) in chronic obstructive pulmonary disease (COPD) patients which are new users of Trimbow (formoterol, glycopyrronium bromide and beclomethasone) administered via dry powder inhaler (DPI) compared to new users of Trimbow administered via pressurized metered dose inhaler (pMDI).
This PASS will be a non-interventional multi-country cohort study among patients with COPD, aged 40 years or older exposed to Trimbow DPI (drug of interest) or Trimbow pMDI (comparator), based on retrospectively collected secondary data derived from different European data sources in the following countries: Denmark, Finland, Germany, the Netherlands, Norway, Sweden, and the United Kingdom. Patients in the two exposure groups will be followed for the study outcomes from the start of exposure until the first occurring of end of treatment, switch to the other study drug, end of study period, or censoring.
The study period is defined to start at the date of the first launch of Trimbow DPI and its market availability (first launch occurred in August 2021) and end on December 31, 2026.
Country-level unadjusted and adjusted IRs (calculated using weighted Poisson regression) of MACE will be estimated separately in the two exposure groups (Trimbow DPI and Trimbow pMDI). To compare the incidence of MACE between the exposure groups, a meta-analysis will be conducted based on the data-source level incidence rate ratios (IRRs). In each data source, unadjusted and adjusted IRRs of MACE and their 95% confidence intervals will be estimated using Poisson regression. A set of sensitivity analyses will be performed to assess different assumptions regarding patient selection, exposure definition, and analytical approach.
The primary outcomes: major cardiovascular events; a composite outcome including myocardial
Infarction; stroke; hospitalization due to acute coronary syndrome; and hospitalization due to heart
failure.
The secondary outcomes will be each of the following specific events: myocardial infarction;
cerebrovascular disorders; hospitalization due to acute coronary syndrome; hospitalization due to
heart failure; arrhythmia; and all-cause death.
Fabian Hoti - Chief Investigator - IQVIA Finland Oy
Micaela Haapanen - Corresponding Applicant - IQVIA Finland Oy
Carlos Lopez - Collaborator - IQVIA Finland Oy
Clare Flach - Collaborator - IQVIA Ltd ( UK )
Emanuil Markov - Collaborator - IQVIA Solution Bulgaria EOOD
Farokh Master - Collaborator - IQVIA Ltd ( UK )
Giorgi Tskhvarashvili - Collaborator - StatFinn Estonia OU
Josephine Dufitinema - Collaborator - IQVIA Finland Oy
Mai Vu - Collaborator - IQVIA Finland Oy
Muriel Lobier - Collaborator - IQVIA Finland Oy
Niina Leinonen - Collaborator - IQVIA Finland Oy
René Cordtz - Collaborator - IQVIA Solutions Denmark AS
Vasili Mushnikov - Collaborator - IQVIA Finland Oy
Henrik Svanström - Collaborator - IQVIA Solutions Denmark AS
Katarzyna Derwinska - Collaborator - IQVIA
Lazar Colic - Collaborator - IQVIA AG (Switzerland)
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation