Chronic obstructive pulmonary disease (COPD) is a respiratory condition with continuing loss of lung function, leading to symptoms such as shortness of breath. Symptoms may become rapidly worse in a short period of time - an event known as an exacerbation. Most patients can be managed using one or two long-acting inhaled drugs (bronchodilators) that dilate the airways in different ways. Triple therapy - containing inhaled steroids and two types of bronchodilator - is the most intensive type of treatment, but it is uncertain whether patients do better on triple therapy compared to therapy with two bronchodilators only. More evidence is needed so that clinicians can make informed treatment decisions for their patients. The proposed study will use information observed in anonymous primary care records of COPD patients to compare the number of exacerbations experienced by patients who were prescribed triple therapy and patients prescribed dual bronchodilator therapy. The study will also investigate whether triple therapy slows the loss of lung function more so than dual bronchodilation, and will explore whether the treatment comparisons are influenced by how severe the COPD symptoms are to begin with, or by the way in which the therapy is delivered.
Two designs will be used to study the effectiveness of triple therapy [TT] (inhaled corticosteroids (ICS) with long-acting muscarinic antagonist and beta agonist [LAMA+LABA]) in COPD patients with a history of smoking: A. Patients who step-up from LAMA+LABA to TT will be compared with patients who remain on LAMA+LABA B. Patients who step-up from LAMA to TT will be compared with patients who step up to LAMA+LABA Primary outcomes: 1. COPD exacerbations: number in first year and time to first event 2. Average decline in forced expiratory volume in first second [FEV1] per year The study uses a historic cohort design, and matches the patients between treatment groups, according to relevant demographic and clinical characteristics. A one year baseline period is used to identify variables for matching, and patients are followed up during an outcome period of at least one year. Exacerbations will be compared using conditional negative binomial regression to estimate the adjusted rate ratios with 95% confidence intervals. Stratified Cox regression will be used to compare the time to first exacerbation. The change in FEV1 over time will be analysed using a multilevel regression model. Effect modification by patient and therapy characteristics will be studied by including interaction-terms.
Primary outcome (Objectives 1 &2): Occurrence of COPD exacerbation; Secondary outcome: Occurrence of acute courses of oral corticosteroid; Secondary outcome: Occurrence of pneumonia diagnosis; Primary outcome (Objective 3): Average decline in forced expiratory volume in first second (FEV1) per year of follow-up; Secondary outcome: Occurrence of antibiotic prescription following lower respiratory consultation; Secondary outcome: Occurrence of hospitalisation with COPD as primary diagnosis; Secondary outcome: mMRC score within 18 months after index date; Secondary outcome: Occurrence of time to first A&E attendance related to COPD.
David Price - Chief Investigator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Marjan Kerkhof - Corresponding Applicant - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Jaco Voorham - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Janwillem Kocks - Collaborator - University Medical Centre Groningen
Mario Scuri - Collaborator - Chiesi
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;Practice Level Index of Multiple Deprivation