Clinical trial NCT06282861: ANTES B+ Clinical Trial
Official title: The ANTES B+ Study: An Open-label, Pragmatic, Randomized, Controlled Trial of Triple Therapy Versus LABA-LAMA Combination to Improve Clinical Control in High Risk GOLD B Patients (B+)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
ECOPD
eosinophil
Trelegy
Clinical Control
Lead sponsor: Fundacio Privada Mon Clinic Barcelona
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2024-02-28
Enrollment: 1028
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase IV, open-label, prospective, pragmatic, interventional, randomized (1:1), multicenter, controlled, 12-month follow-up trial.
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Control (CC)
timeFrame: 3,6,9 and 12 months
Secondary outcomes:
measure: Clinical Important Deterioration (CID)
timeFrame: 3,6,9 and 12 months
measure: Patients persistently controlled
timeFrame: 3,6,9 and 12 months
measure: Time to deterioration
timeFrame: 3,6,9 and 12 months
measure: Time to no control event of CC - Stability Domain
timeFrame: 3,6,9 and 12 months
measure: Time to no control event of CC - Impact Domain
timeFrame: 3,6,9 and 12 months
measure: Time to deterioration event of CID-CAT Exacerbations
timeFrame: 3,6,9 and 12 months
measure: Time to deterioration event of CID-CAT Spirometry
timeFrame: 3,6,9 and 12 months
measure: Exacerbation rate
timeFrame: 3,6,9 and 12 months
measure: Time to first Exacerbation
timeFrame: 3,6,9 and 12 months
measure: Spirometry changes
timeFrame: 3,6,9 and 12 months
measure: Independent predictors
timeFrame: 3,6,9 and 12 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona
state: Catalunya
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Àlvar Agustí
role: PRINCIPAL_INVESTIGATOR
References: