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

(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 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.

This study has been transitioned to CTIS with ID 2023-508300-37-00 check the CTIS register for the current data.

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). 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. Additionally, we aim to 1)
identify characteristics that predict positive additional response to triple
therapy above dual bronchodilator therapy. Effectiveness is defined as
improvement in CCQ of >=0.4 from baseline to follow-up; 2) To compare the number
of moderate and severe exacerbations before (6 months) and during the study (6
months) between the study groups; 3) compare the proportion of patients with
clinically relevant improvement on either CCQ (>=0.4) or ACQ (>=0.5) between the
study groups; 4) To compare the proportion of net responders (positive
responders (>=0.4 improvement on the CCQ) minus negative responders (<=0.4
decline on the CCQ)) between the study groups; 5) compare the difference in
lung function measures, Eos and FeNO between the study groups; 6) describe the
patient reported side effects using the inhaled corticosteroids side-effects
questionnaire Short Form (ICQ-S); 7) investigate the difference in health
resource use and costs between the study groups; 8) investigate the differences
in genome-wide expression of ribonucleic acid (RNA) (messenger (mRNA) and micro
(MiRNA)) and methylation status in epithelial cells derived from nasal
brushings between the study groups; 9) compare the properties of the CCQ and
the COPD Assessment Test (CAT) over the study period;10) investigate the
difference in the pneumonia incidences between the study groups; 11) validate
the role of matrix proteins in the pathological processes in COPD to identify
therapeutic targets for intervention and examine their utility as biomarkers
for monitoring and predicting disease progression and/or treatment response
between the study group between the study groups; 12) investigate whether
presence of a single nucleotide polymorphisms (SNPs) or combination of SNPs can
a) help to predict if COPD patients respond favorably to ICS, and b) influence
expression level of a COPD relevant gene, i.e. are expression quantitative
trait loci.

This is a prospective, real-life, randomised controlled trial of 26 weeks,
which is conducted in general practices and hospitals 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
randomised (1/1) either to the triple therapy arm or the LABA/LAMA treatment
arm.

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.

Participating in the study requires two visits to the patient*s primary care
practice/hospital. One at the start of the study and one after 26 weeks. During
both visits* patients will be requested to complete questionnaires and perform
lung function tests. Additionally, blood eosinophil counts are measured using a
point-of-care test (finger prick) and if consented by the patient a nasal
brushing is performed. At the first visit patients are referred to a location
of the primary care laboratory for an IgE blood test. In the end, it is
expected that triple therapy reduces respiratory symptoms and the number of
exacerbations and hospitalizations in COPD patients. Pneumonia has been
reported as a common, major side effect of ICS in COPD patients. However, this
applies to COPD patients in general, it is not known if pneumonia frequently
occurs in COPD patients with asthma characteristics (our study population).