Clinical trial NCT05919394: Triple vs High Dose Inhaled CORticosteroids
Official title: Increase in Inhaled Corticosteroid Dose vs Triple Therapy in T2-high Asthma Patients Who Remain Uncontrolled With Medium Dose Inhaled Corticosteroids/Long-acting β2 Adrenergic Combination: a Real-life Study. TRICORDA Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Asthma
Keywords: Wheezing
Dyspnoea
Cough
Lead sponsor: Galaxia Empírica
Sponsor class: NETWORK
Collaborators: name: Sociedad Española de Neumología y Cirugía Torácica
First posted: 2023-06-26
Enrollment: 620
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Increase in inhaled corticosteroid dose vs triple therapy in T2-high asthma patients who remain uncontrolled with medium dose inhaled corticosteroids/long-acting β2 adrenergic combination: a real-life study.

Detailed description: It remains to be clarified whether triple therapy is better than high dose inhaled corticosteroids and long-acting beta2-agonists combination (ICS/LABA) in patients with uncontrolled asthma despite the use of medium dose ICS/LABA combinations, particularly in cases with high T2 biomarkers´ values. The aim of this study is to evaluate, in a real-world setting, which is the best therapeutic strategy in this clinical scenario.

This study will be a randomized, open-label, two-arm, prospective, 12-month trial to be conducted in 53 hospital asthma units. Participants will be allocated to receive one of two therapeutic strategies: same ICS/LABA combination at highest doses or the same maintenance therapy plus a long-acting anticholinergic (LAMA). Follow up visits will be scheduled at 12-16, 24-28 and 52 weeks after the baseline visit. The investigators can optimise therapy according to their clinical opinion if the patient remains uncontrolled. Demographic, clinical and lung function information will be collected at each visit.

The primary endpoint will be the percentage of patients controlled at week 52, with both an ACT score of 20 or greater and no severe exacerbations). 620 patients (282 patients per treatment group, considering 10% drop-out) will be required for the study to have 80% power to detect non-inferiority limit of 10% in the rate of controlled patients between the high dose ICS/LABA arm and the triple therapy arm. All effectiveness analyses will be done according to the intention-to-treat principle. Secondary endpoints: percentage of patients controlled at week 24, ACT at weeks 12, 24 and 52, AIRQ at weeks 12, 24 and 52, quality of life (Mini-AQLQ) at weeks 12, 24 and 52, postbronchodilator FEV1 at weeks 12, 24 and 52, severe exacerbations at week 24 and 52. Differences between groups in 8 AM serum cortisol at week 52. Adherence at week 52 in the two study arms. Factors related to triple and high-dose ICS/LABA failure and success (control) at week 52.

The results of this study will help physicians to decide the most appropriate therapeutic strategy for a large number of asthma patients: those who do not gain control with medium dose ICS/LABA. If non-inferiority of triple therapy vs high dose ICS/LABA is demonstrated, it could lead to a modification of the current guidelines.

Eligibility criteria: Inclusion Criteria:

* Patients between 18 and 80 years of age diagnosed of uncontrolled asthma.
* T2 high asthma: \> 300 cels/mm3 blood Eos (current value) or 150 cels/mm3 blood Eos (current value) and a historical value ≥ 300 cels/mm3 or FENO ≥ 25 ppb (current value).
* Uncontrolled asthma, this is, ACT \<20 and/or \> 1 of an exacerbation in the last 12 months, despite treatment with ICS/LABA at medium dose.
* Written informed consent.

Exclusion Criteria:

* Patients who refuse to sign the informed consent form.
* Medical situation that prevents the collection of study information.
* Diagnosis of severe uncontrolled asthma established with criteria other than those established (ACT \<20 and/or \> 1 exacerbation in the last 12 months, despite treatment with ICS / LABA at medium dose).
* Medical or administrative situation that prevents the patient from following up to a minimum of 52 weeks.
* Treatment with high dose ICS/LABA, LAMA, systemic corticosteroid, azithromycin, monoclonal antibody.

Primary outcomes:
measure: The percentage of patients controlled
timeFrame: At 52 weeks
Secondary outcomes:
measure: Percentage of patients controlled
timeFrame: At week 24
measure: ASMA CONTROL TEST (ACT)
timeFrame: At weeks 12, 24 and 52
measure: AIRQ
timeFrame: At weeks 12, 24 and 52
measure: Quality of life (Mini-AQLQ)
timeFrame: At weeks 12, 24 and 52
measure: Postbronchodilator FEV1
timeFrame: At weeks 12, 24 and 52
measure: Severe exacerbations
timeFrame: At week 24 and 52
measure: Differences between groups in 8 AM serum cortiso
timeFrame: At week 52
measure: Adherence in the two study arms
timeFrame: At week 52
measure: Factors related to triple and high-dose ICS/LABA failure and success (control)
timeFrame: At week 52
Other outcomes:
Locations:
city: Inca
country: Spain
facility: Hospital Comarcal de Inca - Tramuntana
state: Baleares
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Barakaldo
country: Spain
facility: Hospital Universitario de Cruces
state: Bizkaia
city: Galdakao
country: Spain
facility: Hospital Universitario Galdakao-Usansolo
state: Bizkaia
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario De Jerez
state: Cádiz
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
state: Navarra
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Valencia
city: A Coruña
country: Spain
facility: Hospital Universitario de A Coruña
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis de Alicante
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Granada
country: Spain
facility: Hospital Universitario Clínico San Cecilio
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Salamanca
country: Spain
facility: Hospital Clínico Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Álaga
Study officials:
affiliation: Sociedad Española de Neumología y Cirugía Torácica
name: Luis Pérez De Llano, MD
role: PRINCIPAL_INVESTIGATOR
References: