Triple therapy effectiveness in COPD patients with characteristics of asthma: A pragmatic primary care trial - The TRACkER trial

Rationale: (Inter)National guidelines identify several patient characteristics that can be used to select patients with Chronic Obstructive Pulmonary Disease (COPD) who may benefit from inhaled corticosteroids (ICS) containing treatment. These characteristics include asthma characteristics, high blood eosinophil (Eos) counts and frequent exacerbations (despite the usage of a bronchodilator). However, this evidence was originally based on post hoc analysis from randomised controlled trials. Little is known regarding the utility of these characteristics in real life, as tools for guiding doctor’s decision to prescribe ICS containing medication in routine practice.

Objective: To investigate the effectiveness of triple therapy (ICS/ long-acting beta 2 agonist (LABA)/long-acting muscarine antagonist (LAMA)) on the change in health status, measured with the Clinical COPD Questionnaire (CCQ), in symptomatic ICS-naive COPD patients with characteristics of asthma according to GOLD 2019 and blood eosinophil counts of ≥100 cells per µL compared to treatment with dual therapy (LABA/LAMA), within a primary care population. Effectiveness is regarded as difference in the proportion of patients with a minimal clinically improvement on health status (CCQ improvement ≥0.4) between the study groups.

Study design: This is a prospective, real-life, randomised controlled trial of 26 weeks, which is conducted in general practices in the north of the Netherlands comparing triple therapy (ICS/LABA/LAMA) with dual bronchodilator treatment (LABA/LAMA). We aim to randomise 316 patients. Patients will be randomized (1/1) either to the triple therapy arm or the LABA/LAMA treatment arm.

Study population: ICS-naive symptomatic (CCQ≥1) primary care COPD patients aged over 40 years who are currently using one or two long-acting bronchodilators with characteristics of asthma (age of onset <20 years; day to day variation in symptoms or symptoms which are worse during the night/early morning; history of asthma, allergy, rhinitis, eczema) and a blood eosinophil count of ≥100 cells per µL.

Intervention: In the intervention group patients will use a single inhaler triple therapy (Trimbow), which includes a combination of beclomethasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide. This inhaler is used twice a day. In the control group patients will use dual bronchodilator treatment (LABA/LAMA) which is used according to the prescription.

Main study parameters/endpoints: The primary outcome of this study is the difference in the proportion of patients with a clinically relevant improvement in health status (≥0.4 improvement on the CCQ) between the triple therapy group and LABA/LAMA treatment groups at the end of the 26 weeks intervention period. All main analyses will be conducted intention-to-treat.

It is expected that patients in the triple therapy group improve their health status (CCQ score) more than the patients in the LABA/LAMA group.

Study start: 02-12-2019
Start inclusion: 16-12-2019
Study period: 26 weeks/6 months
End inclusion period: 01-07-2019

In the intervention group patients will use a single inhaler triple therapy (Trimbow), which includes a combination of beclomethasone dipropionate, formoterol fumarate dihydrate, and glycopyrronium bromide. This inhaler is used twice a day. In the control group patients will use dual bronchodilator treatment (LABA/LAMA) which is used according to the prescription.