Clinical trial NCT05831566: Expertise Asthma COPD Program with Digital Support
Official title: Expertise Asthma COPD Program with Digital Support
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Asthma
Keywords: severe asthma
ehealth
digital home monitoring
difficult to treat asthma
treatable traits
assessment
biologics
Lead sponsor: Franciscus Gasthuis
Sponsor class: OTHER
Collaborators: name: Teva Pharmaceuticals USA
First posted: 2023-04-26
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, randomized controlled trial with a superiority design. Patients will be randomly assigned to one of two groups in parallel for the duration of the study. They will either recieve biologics directly or they will undergo an in-dept assessment to map the asthma diagnosis in more detail.
Primary purpose: TREATMENT

Brief summary: The aim EXACT@Home is to create an evidence-based health program using e.g. questionnaires, a digital health platform and multiple digital devices to further improve the assessment of patients diagnosed with severe asthma. By better charting treatable traits (e.g. poor adherence, physical inactivity, dysfunctional breathing), we expect to improve the indication for the use of biologics. One the devices that will be used is also a medicinal product: a digital inhaler, which monitors adherence and inhaler technique through its connected application and aims to improve adherence and inhaler technique with reminders and notifications. Next to this an activity tracker, hand-held spirometer and FeNO measuring device will be used. The information of the devices will be collected in a Personal Digital Healthcare Environment (PDHE). Patients diagnosed with severe asthma according to the regional asthma Multi-Disciplinary Team Meeting (MDTM) eligible for a treatment with biologics will be included. Half of the patients will immediately receive a biologic. The other half will first undergo the systematic assessment including home monitoring (=EXACT@home) and afterwards a treatment will be chosen based on this evaluation: optimization of treatable traits when present and/or biologics. The chosen treatment of both, the intervention and control group, will be evaluated during 11-12 months.

Detailed description: Rationale:

Asthma is a common multifactorial disease with chronic inflammation of the lower airways, which is in most cases adequately treated by inhalation medication. 17% of asthma patients have difficult-to-treat asthma, which is uncontrolled despite of an optimal treatment with medication due to the presence of 'treatable traits'. Examples of treatable traits are poor adherence to ICS/LABA therapy and inhaler technique, dysfunctional breathing, physical inactivity and behavior. Severe and refractory asthma is a subtype of difficult-to-treat asthma and only occurs if the asthma is uncontrolled despite optimized treatment with medication and addressing of treatable traits, which occurs in only 3.7% of all asthma patients. This group of patients is responsible for a high burden of overall disease, as well as large healthcare costs.Treatment options with biologics have fundamentally changed the care for patients with severe asthma by giving a relevant improvement in asthma control, the number of asthma exacerbations and quality of life. On the other hand, these drugs are also very expensive and must be given for the correct indication.

The Centre of Excellence for severe Asthma, Franciscus Gasthuis \& Vlietland, Rotterdam organizes a weekly Multi-Disciplinary Team Meeting (MDTM) for hospitals in the South-West of the Netherlands to discuss their patients with problematic asthma and to start a treatment with biologics approved for severe asthma (in this document further called biologics). Despite maximal efforts of all stakeholders, the complete overview of a patient and the treatable traits is often hampered by the complexity and heterogeneity of severe asthma.

The aim of the EXACT@Home (Expertise Asthma COPD program with digital support) study is to further improve the assessment of treatable traits using ehealth before considering treatment with biologics.

Objectives:

Primary objective: To investigate if the EXACT@home program results in a reduced percentage of patients treated with biologics by means of systematically targeting treatable traits measured after 6 months of follow up.

Secondary objectives: To determine whether the use of EXACT@home results in a reduced percentage of patients treated with biologicals after 11-12 months. Next to this it will be investigated if EXACT@home has an influence on quality of life, asthma control, dyspnea perception, lung function, exacerbation frequency, prednisolone use, direct healthcare consumption, self-management skills, patient satisfaction, adherence to ICS/LABA therapy and inhaler technique, physical activity, sleep and vital parameters. Next to this, breath pattern analysis will be performed with the electronic nose (eNose). Moreover, the safety of the Digital inhaler (BF-Digihaler-DS from Teva) and eNose (Spironose from Breathomix) and the course of the treatment in each patient will also be investigated.

Study design:

Open-label, randomized controlled trial with a superiority design.

Study population:

Patients aged ≥ 18 years, in which the diagnosis severe and refractory asthma and eligibility for treatment with biologics was determined at the regional asthma MDTM will be asked to participate in this project.

Intervention (if applicable):

Patients will be randomized in 2 groups (intervention - and control group). The intervention group participates in a holistic assessment called EXACT@home consisting of a period of 6 weeks addressing diagnosis, asthma phenotype and treatable traits using e.g. questionnaires and digital devices measuring airway obstruction, eosinophilic airway inflammation, adherence to ICS/LABA therapy, inhalation technique, movement, vital parameters and sleep. The information of the devices and all other information concerning the patient will be stored in an 'Personal Digital Healthcare Environment (PDHE)'. Afterwards the collected data will be evaluated. Based on this evaluation and the degree of asthma control the type of treatment will be determined: optimization of 'treatable traits' or start of treatment with biologics. The control group will immediately start the treatment with biologics. The chosen treatment of both, the intervention and control group, will be evaluated during 11-12 months.

Main study parameters/endpoints:

Study parameter primary outcome:

Difference between the intervention and control group in the percentage of patients treated with biologicals after 6 months of follow up.

Study parameters secondary outcome:

The percentage of patients treated with biologicals after 11-12 months of follow up, quality of life, asthma control, dyspnea perception, lung function, exacerbation frequency, prednisolone use, direct healthcare consumption, self-management skills, patient satisfaction, adherence to ICS/LABA therapy, inhaler technique, physical activity, slap, vital parameters, breath pattern analysis with the eNose, safety of the digital inhaler and eNose and the course of the treatment in each patient.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

The possible burden of the intervention group is temporarily postponing an effective treatment with biologics in favour of in depth extensive assessment in patients with a severe disease for a short period of at least 6 weeks. On the other hand, the patient could benefit from the EXACT@home assessment possibly leading to a personalized treatment, in which a treatment with biologics might not be necessary anymore. Next to this, another possible minor burden is 1 extra visit in addition to standard care.

Eligibility criteria: Inclusion criteria:

* Confirmed asthma diagnoses (≥12% and \>200 ml reversibility in FEV1 or positive histamine/methacholine provocation test or FeNO ≥50) according to the asthma guidelines
* Diagnosed with severe, refractory asthma with eligibility for treatment with specific asthma biologics (omalizumab, mepolizumab, benralizumab, reslizumab, dupilumab) as determined at the regional asthma MDTM according to the asthma guidelines
* Age ≥ 18 years.
* Previous prescribed asthma biologics have to be ceased ≥ 4 times the half-life of that specific biologic.
* The patient has be relatively stable. The onset of an asthma exacerbation and/or a respiratory infection has to be ≥ 4 weeks ago.

Exclusion criteria:

* Primary COPD diagnosis.
* History of cancer:

  * Current basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to the start of the study.
  * Current other malignancies. Patients are eligible to participate in the study provided that curative therapy was completed at least 5 years prior to the start of the study.
* Inability to sufficiently understand and read the Dutch language.
* Being unable to engage in a remote monitoring and coaching program through the use of a smartphone.
* Being unable to engage in physical activity (e.g. physical disability).
* Current pregnancy.
* Current breastfeeding.
* A liaison with the coordinating or (principal) investigator, which could likely influence the decision to participate in this study voluntarily (in concordance with the WMO - article 5).

Primary outcomes:
measure: Difference in percentage of patients treated with biologicals after 6 months of follow up
timeFrame: 6 months
Secondary outcomes:
measure: Difference in percentage of patients treated with biologicals after 12 months of follow up
timeFrame: 12 months
measure: Difference in change in asthma control over time between the intervention- and control group
timeFrame: 6-12 months
measure: Difference in change in quality of life over time between the intervention- and control group
timeFrame: 6-12 months
measure: Difference in asthma exacerbation frequency
timeFrame: 6-12 months
Other outcomes:
measure: Difference in change in spirometry and FeNO over time between the intervention - and control group.
timeFrame: 6-12 months
measure: Difference in direct healthcare consumption between the intervention- and control group
timeFrame: 6-12 months
measure: Difference in prednisolone courses between the intervention- and control group.
timeFrame: 6-12 months
measure: Difference in reduction in prednisolone maintenance therapy (if applicable) between the intervention and control group
timeFrame: 6-12 months
measure: Difference in cumulative prednisolon dosage between the intervention- and control group.
timeFrame: 6-12 months
measure: Difference in self-management between the intervention- and control group.
timeFrame: 6-12 months
measure: Difference in dyspnea perception between the intervention- and control group.
timeFrame: 6-12 months
measure: Difference in wellbeing between the intervention- and control group
timeFrame: 6-12 months
measure: Difference in patient satisfaction between the intervention- and control group
timeFrame: 6-12 months
measure: Measuring the change over time in physical activity in the intervention group
timeFrame: 6-12 months
measure: Measuring the change over time in adherence and inhaler technique in the intervention group and the control group seperately
timeFrame: 6-12 months
measure: Observing sleeping patterns in the intervention group
timeFrame: 6-12 months
measure: Observing vital parameters in the intervention group.
timeFrame: 6-12 months
measure: Measuring the differences in VOCs in exhaled breath measured with the eNose between baseline and follow-up in the intervention and in the control group separately.
timeFrame: 6-12 months
measure: Monitoring of safety of the Digital inhaler (BF-Digihaler-DS from Teva) and eNose (Spironose from Breathomix).
timeFrame: 6-12 months
measure: Monitoring and recording the course of treatment of each patient including the explanation behind changes in treatment (e.g. stopping treatment with biologicals).
timeFrame: 6-12 months
Locations:
city: Rotterdam
country: Netherlands
facility: Franciscus Gasthuis &amp; Vlietland
state: Zuid-Holland
Study officials:
affiliation: Franciscus Gasthuis &amp;amp;amp; Vlietland
name: J.C.C.M. In &amp;amp;#39;t Veen, dr.
role: PRINCIPAL_INVESTIGATOR
References: