Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, ECOPD, eosinophil, Trelegy, Clinical Control
Brief summary
Current guidelines recommend initial treatment with dual long-acting bronchodilator therapy (LABA-LAMA) in patients with Chronic Obstructive Pulmonary Disease (COPD) of group B (defined by CAT≥10 and none or 1 moderate exacerbation). However, the investigators hypothesize that there is a subgroup of B patients (B+) at a particularly high risk for poor clinical control, characterized by the following: * 1 moderate exacerbation in the previous year * CAT≥10 despite current treatment with LABA -LAMA * Blood eosinophil levels of ≥150 cells/ml the investigators further hypothesize that B+ patients could benefit from triple therapy treatment (LABA-LAMA + Inhaled Corticosteroids). Therefore, the main goal of this clinical trial is to compare the efficacy of Trelegy (triple therapy) in improving clinical control in GOLD B+ patients with chronic obstructive disease when compared to standard double therapy (LABA -LAMA). The clinical control is a validated composite endpoint that includes two domains, the patient's stability, and the impact of the disease. 1028 patients will be randomly allocated to receive either the standard therapy or Trelegy and will be monitored by the investigators for 1 year in 2 on-site visits + 2 remote visits.
Interventions
Product to be used according to specifications. 1 inhalation daily for 12 months
DRUGBrimica
As per product specifications
DRUGDuaklir
As per product specifications
DRUGUltibro
As per product specifications
DRUGUlunar
As per product specifications
DRUGXoterna
As per product specifications
DRUGAnoro
As per product specifications
DRUGLaventair
As per product specifications
DRUGSpiolto Respimat
As per product specifications
DRUGYanimo
As per product specifications
DRUGForadil
As per product specifications
DRUGBroncoral
As per product specifications
DRUGFormoterol stada
As per product specifications
DRUGOxis
As per product specifications
DRUGFormatris
As per product specifications
DRUGFormoterol Aldo
As per product specifications
DRUGOnbrez
As per product specifications
DRUGOslif
As per product specifications
DRUGHirobriz
As per product specifications
DRUGStriverdi
As per product specifications
DRUGBeglan
As per product specifications
DRUGBetamican
As per product specifications
DRUGInaspir
As per product specifications
DRUGSerevent
As per product specifications
DRUGSoltel
As per product specifications
DRUGEklira
As per product specifications
DRUGBretaris
As per product specifications
DRUGSeebri
As per product specifications
DRUGTovanor
As per product specifications
DRUGEnurev
As per product specifications
DRUGSpiriva
As per product specifications
DRUGTavulus
As per product specifications
DRUGSirkava
As per product specifications
DRUGBraltus
As per product specifications
DRUGGregal
As per product specifications
DRUGIncruse
As per product specifications
DRUGRolufta
As per product specifications
Sponsors
GlaxoSmithKline
Fundacio Privada Mon Clinic Barcelona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Phase IV, open-label, prospective, pragmatic, interventional, randomized (1:1), multicenter, controlled, 12-month follow-up trial.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Female or male * 40-80 yrs. of age * Current/former smokers ≥10 pack-year * Diagnosis of COPD according to GOLD 2023 (post-bronchodilator(BD) FEV1/FVC\<0.7 in the appropriate clinical context) with FEV1 post-BD 30-70% of the reference value * B+ phenotype * CAT≥10 despite being on LABA-LAMA for ≥3 months, and * 1 moderate ECOPD in the previous year (treated with a short course of oral steroids and/or antibiotics), and * ≥150 blood Eos/ μL (as determined by a single Eos measurement in the previous 12 months available in the medical record of the patient) * A signed and dated written informed consent prior to study participation.
Exclusion criteria
* GOLD E (≥2 moderate or 1 severe ECOPD in the previous year) * ICS treatment (or oral steroid for whatever reason) during the last 8 weeks (10) * ECOPD during the last 8 weeks * Current diagnosis of asthma or documented history of asthma in the medical record of the patient according to the 2023 Global Initiative for Asthma (GINA) guidelines or other accepted guidelines * Other concomitant respiratory disease (e.g., bronchiectasis, lung fibrosis, lung neoplasm) * Use of domiciliary long-term oxygen therapy or non-invasive ventilation * Alpha-1 antitrypsin deficiency * Unstable or life-threatening cardiac disease, including: * Myocardial infarction or unstable angina in the last 6 months * Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 3 months. * New York Heart Association (NYHA) Class IV Heart failure. * Participation on Pulmonary Rehabilitation Program within 4 weeks prior to Screening or subjects who plan to enter the acute phase of a Pulmonary Rehabilitation Program during the study. * Long term antibiotic therapy (antibiotics are allowed for the short-term treatment of an exacerbation or for short term treatment of other acute infections during the study). * Systemic, oral, parenteral corticosteroids used for COPD and/or other diseases in the 8 weeks before entering in the study (oral/systemic corticosteroids may be used to treat COPD exacerbations during the study). * Active neoplasm * Life expectancy \< 1 yr. * Current participation in other RCTs (randomized clinical trial) * Non-compliance: subjects at risk of non-compliance, or unable to comply with the study procedures. * Any disease, disability, or geographic location that would limit compliance for scheduled visits. * Known allergy to Trelegy® components (vilanterol, umeclidinium and/or fluticasone furoate) or inability to use the Ellipta® device. * Women who are pregnant or lactating or are planning to become pregnant during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Control (CC) | 3,6,9 and 12 months | Patient persistently controlled by CC at all study visits (a subject to be categorized as having clinical control they must meet the criteria at month 3, 6, 9 and 12). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients persistently controlled | 3,6,9 and 12 months | Patients persistently controlled (at all visits) throughout the study between the two study arms as per: * CC - Stability Domain 1. General status since the last visit 2. Exacerbations in the last 3 months * CC - Impact Domain 1. Sputum color 2. Rescue medication use 3. Minutes walked per day 4. Dyspnea (mMRC) * CID-CAT - Exacerbations * CID-CAT - (Patient reported outcomes)PROs * CID-CAT - Lung function |
| Time to deterioration | 3,6,9 and 12 months | time to first event of not being CC or suffer CID-CAT |
| Time to no control event of CC - Stability Domain | 3,6,9 and 12 months | Time to first no control event for CC - Stability Domain |
| Time to no control event of CC - Impact Domain | 3,6,9 and 12 months | Time to first no control event for CC - Impact Domain |
| Time to deterioration event of CID-CAT Exacerbations | 3,6,9 and 12 months | Time to deterioration event for CID-CAT Exacerbations |
| Clinical Important Deterioration (CID) | 3,6,9 and 12 months | Patients persistently non deteriorated by CID-CAT at all study visits.(a subject to be categorized as having control by CID-CAT they must meet the criteria a month 3, 6, 9 and 12). |
| Exacerbation rate | 3,6,9 and 12 months | To compare several Health status related endpoints between study arms including: d.To evaluate the mean and annual rate of: * Moderate exacerbations (ECOPD) * Severe ECOPD (hospitalized) * Moderate and Severe ECOPD |
| Time to first Exacerbation | 3,6,9 and 12 months | To compare several Health status related endpoints between study arms including: e.To evaluate time to first ECOPD including: * Moderate ECOPD * Severe ECOPD (hospitalized) * Moderate or Severe ECOPD |
| Spirometry changes | 3,6,9 and 12 months | To compare several Health status related endpoints between study arms including: f. To assess annual FEV1(Forced Expiratory volume) and FVC (forced vital capacity) changes (ml/year) |
| Independent predictors | 3,6,9 and 12 months | Independent predictors with a potential negative impact on achieving the CC, each of its domains and each of its variables at each study visit. |
| Time to deterioration event of CID-CAT Spirometry | 3,6,9 and 12 months | Time to deterioration event for CID-CAT Spirometry |
Countries
Spain
Outcome results
None listed