Clinical trial NCT06360393: Inhaler Adherence and Inhalation Technique Assessed by a Smart Spacer in Patients with Severe Asthma on Biologics
Official title: Inhaler Adherence and Inhalation Technique Assessed by a Smart Spacer in Patients with Severe Asthma on Biologics
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Asthma
Keywords: Severe asthma
Biologics
Digital home monitoring
Digital spacer
Adherence
Inhalation technique
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Trudell Medical International
First posted: 2024-04-11
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants aged over 18 years, diagnosed with severe asthma by a physician according to GINA guidelines. They must be using a biologic medication (omalizumab, mepolizumab, reslizumab, benralizumab, or dupilumab) and medium or high dose ICS + LABA with or without LAMA and/or SABA via pMDI and spacer.

Brief summary: Severe refractory asthma affects about 3.5% of asthma patients, often necessitating biologic therapy in addition to standard treatment. However, little is understood about maintenance and reliever inhalation medication adherence in these cases which might impact overall biologic response. Objectively monitoring inhalation medication adherence remains a significant challenge. The Smart AeroChamber® device, capable of measuring adherence and inhalation technique, is untested in severe asthma patients on biologics, presenting a potentially cost-effective solution to monitor adherence and better understand treatment response.

This study aims to assess the feasibility of the Smart AeroChamber® device in severe asthma patients on biologic therapy, with objectives to:

1. Evaluate inhalation medication adherence patterns and inhaler technique, and comparing that adherence data with traditional measures e.g. the Test of Adherence to Inhalers (TAI), and an inhalation technique checklist.
2. Investigate the association between inhaled medication adherence and clinical outcomes such as exacerbations, short-acting beta-agonists (SABA) use, oral corticosteroids use (OCS), Fractional Exhaled Nitric Oxide (FeNO), blood eosinophil count, and Asthma Control Questionnaire (ACQ) scores.
3. Assess patient and healthcare provider satisfaction and usability of the Smart AeroChamber® device.

The study design is prospective and observational, with a sample size of 110 adult patients diagnosed with severe asthma using biologic therapy. Participants will be followed for 12 months, during which they will receive Smart AeroChamber® devices. These devices will measure medication adherence and inhaler technique, and undergo assessments of clinical outcomes at regular intervals. Usability and satisfaction will also be evaluated using the Systems Usability Scale (SUS) in patients and healthcare professionals.

The study will be conducted across five severe asthma clinics in the Netherlands. Data analysis will involve comparing the inhalation medication adherence data with traditional measures for adherence and inhalation technique, assessing clinical outcomes, and evaluating usability and satisfaction. The findings from this study will provide insights into the feasibility and effectiveness of using digital devices like the Smart AeroChamber® to support medication adherence and possibly improve outcomes in patients with severe asthma on biologic therapy.

Detailed description: Rationale:

Despite the availability of effective inhaled medications, 15% of asthma patients remain uncontrolled on medium to high dose inhaled corticosteroids (ICS) and LABA, comprising difficult-to-treat asthma and severe refractory asthma groups. GINA guidelines stress the importance of assessing adherence and technique before step-up treatment due to associated risks and costs.

Research underscores the efficacy and cost-effectiveness of investing in adherence and technique support, particularly in this population. However, there is limited understanding of ICS adherence during biologic therapy, despite its increasing use. Studies on biologics like mepolizumab suggest associations between ICS adherence and improved outcomes, while data on others like benralizumab are less conclusive.

Indeed, non-adherence and poor technique is widely reported in patients with all severities of asthma and is associated with increased morbidity and economic burden. Objectively assessing and enhancing adherence remains one of the major challenges for physicians, pharmacists and nurses. Limited studies on digital tools for adherence management exist, particularly for pMDIs in combination with spacers. Digital technologies are promising in addressing these challenges, but studies on devices capable of objectively measuring adherence and technique, especially in patients using pMDIs, are lacking. The Smart AeroChamber® device presents an innovative solution, showing potential in clinical trials for asthma and COPD. The Smart AeroChamber® is a CE-certified device. However, its application in severe asthma patients on biologics remains unexplored, presenting an opportunity to enhance adherence support and treatment outcomes in this cost-sensitive population.

The aim:

This study aims to evaluate the feasibility of using a Smart Spacer device in patients with severe asthma who are on biologic therapy. The research aims to achieve several objectives:

1. Assess medication adherence patterns and inhaler technique using the Smart Spacer device and compare the data with traditional adherence measures, such as the Test of Adherence to Inhalers (TAI), and an inhalation technique checklist.
2. Evaluate the association between adherence measured by the Smart Spacer device and various clinical outcomes including exacerbations, use of short-acting beta agonists (SABA) and oral corticosteroids (OCS), Fractional exhaled Nitric Oxide (FeNO) results, blood eosinophil count, and asthma control questionnaire (ACQ) scores.
3. Assess the usability and satisfaction of patients and healthcare providers with the Smart Spacer device, using the System Usability Scale (SUS).

Study Design:

This study adopts a prospective, observational design.

Inclusion Criteria:

Participants eligible for inclusion are adults aged over 18 years, diagnosed with severe asthma by a physician according to GINA guidelines. They must be using a biologic medication (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab or tezepelumab) and medium or high dose ICS + LABA with or without LAMA and/or SABA via pMDI in combination with a spacer. Additionally, participants must be willing to provide informed consent.

Exclusion Criteria:

Participants are excluded from participation when they are unable to sufficiently understand and read the Dutch language, being pregnant or being terminally ill.

Sample Size:

The study aims to include a total of 110 patients.

Setting:

The study is conducted in five severe asthma clinics across various regions of the Netherlands (Medical Center Leeuwarden, Martini Hospital Groningen, Isala Zwolle, Sint Franciscus Gasthuis, and University Medical Centrer Groningen).

Baseline Assessment:

Participants undergo characterization during an intake visit to the severe asthma clinic, including demographic data, medical history, spirometry tests, FeNO measurement, blood eosinophil count, ACQ assessment, adherence evaluation using TAI, and inhaler technique assessment via checklist. Subsequently, participants receive two fully charged smart spacers, one for each period of three months, along with instructions for use.

Follow-up:

After 4 weeks, participants are contacted to check the functionality of the smart spacer and receive assistance if needed. A follow-up call at 3-months and 9-months into the study remind participants to switch to the next smart spacer. A physical visit is scheduled at the 6-month mark for further assessment, including ACQ administration and collection of smart spacers for replacement.

End of Study Assessment:

At the end of the 12-month study period, participants undergo a final physical visit for assessment of various parameters including FeNO, blood eosinophil count, lung function, ACQ score, inhaler technique, and documentation of exacerbations and OCS use. Smart spacer data analysis is conducted centrally, and feedback is provided to study sites. Additionally, usability and satisfaction surveys are completed by patients and study nurses.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* 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)
* Using medium or high ICS + LABA +/- LAMA+/-SABA) by pMDI+spacer
* Willing to sign informed consent

Exclusion Criteria:

* The use of the Symbicort Aerosol or the Trixeo Aerosphere in combination with a spacer (these inhalers are not compatible with the smart spacer)
* Inability to sufficiently understand and read the Dutch language
* Current pregnancy
* Currently terminally ill

Primary outcomes:
measure: Comparative analysis of smart spacer medication adherence and inhaler technique against Test of Adherence to Inhalers (TAI-12)
timeFrame: TAI is measured at baseline and 12 months
measure: Comparison of smart spacer medication adherence patterns (adherence and inhaler technique) with inhaler checklist examined by pulmonologist or pulmonary nurse
timeFrame: Inhaler checklist is assessed at baseline and 12 months
Secondary outcomes:
measure: Assessing the association of smart spacer assessed adherence with annual exacerbation rate
timeFrame: Over a period of 12 months
measure: Assessing the association of smart spacer assessed adherence with reliever inhaler use (e.g. SABA)
timeFrame: Over a period of 12 months
measure: Assess the association of smart spacer assessed adherence with oral corticosteroids use
timeFrame: Over a period of 12 months
measure: Assess the association of smart spacer assessed adherence with FeNO results
timeFrame: FeNO is measured at baseline and 12 months
measure: Assess the association of smart spacer assessed adherence with blood eosinophils
timeFrame: Blood eosinophils measured at baseline and 12 months
measure: Assess the association of smart spacer assessed adherence with asthma control (ACQ-6)
timeFrame: ACQ is measured at baseline, 6 months and 12 months
measure: Assess the association of smart spacer assessed adherence with spirometry results
timeFrame: Spirometry is performed at baseline and 12 months
Other outcomes:
measure: Assess usability and patient satisfaction using the System Usability Scale
timeFrame: SUS is measured at 12 months
measure: Assess usability and healthcare provider satisfaction using the System Usability Scale
timeFrame: SUS is measured at 12 months
Locations:
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
state: Friesland
city: Zwolle
country: Netherlands
facility: Isala
state: Overijssel
city: Rotterdam
country: Netherlands
facility: Stichting Sint Franciscus Vlietland Groep
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Groningen
country: Netherlands
facility: Foundation Martini Hospital
Study officials:
affiliation: University Medical Center Groningen
name: Job FM van Boven, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
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