Efficacy of a Smart add-on Device in Combination With a Triple Treatment in Asthma Patients on Inhaler Technique and Adherence

A 52-week, Multicentre, Observational, Prospective Study on the Use of a Smart Platform Connected to a Single-inhaler Triple Therapy (ICS/LABA/LAMA) to Evaluate Effectiveness on Treatment Adherence and Inhaler Technique in Patients With Poorly Controlled Asthma.

The goal of this observational study is to determine if using the SiA® (Systematic Intervention Agent) system can improve inhaler technique and medication adherence in adults with asthma who are already using Trimbow pMDI inhalers. Furthermore, it will be addressed if the SiA® system can be used to discriminate between patients, where increased inflammatory markers are caused by incorrect inhaler technique/adherence to medication or patients that have ongoing inflammation requiring adjustment of therapy. Potentially those who might become candidate for biological treatments.

The main questions it aims to answer are:

• Can the SiA® system improve inhaler use and medication adherence in asthma patients?
• Does improving inhaler technique and adherence lead to better asthma control and reduced airway inflammation (measured by FeNO levels)?

Participants will:

• Use the SiA® system, which includes a smart inhaler cap (RespiPRO™) and a mobile app
• Continue their prescribed Trimbow pMDI treatment for asthma.
• Have their asthma control, lung function, and FeNO levels monitored at specific points over 1 year (3 months and 12 months).

The study does not have a comparison group and all results will be compared to baseline.

Background and Rationale Asthma is a chronic inflammatory disease of the airways that affects millions of individuals worldwide. Despite the availability of effective inhaled medications, poor adherence and incorrect inhaler technique remain major barriers to optimal asthma control. Studies show that up to 86.7% of asthma patients make at least one inhaler technique error, and 30-40% demonstrate poor adherence to their prescribed medication. These factors contribute to worsened symptoms, increased healthcare utilization, and reduced quality of life.

The SiA® system, developed by Briota ApS, aims to address these challenges by integrating a smart inhaler cap (RespiPRO™) with a mobile application. This system provides real-time feedback on inhaler technique and adherence, allowing patients and healthcare providers to track progress and make necessary adjustments.

This study seeks to determine whether using the SiA® system alongside a pressurized metered dose inhaler (pMDI) therapy can lead to measurable improvements in medication adherence, inhalation technique, and asthma control. Furthermore, it will be addressed if the SiA® system can be used to discriminate between patients, where increased inflammatory markers are caused by inadequate treatment caused by incorrect inhaler technique/adherence to medication or patients that have ongoing inflammation requiring adjustment of therapy. Potentially those who might become candidate for biological treatments.

Study Design This is a prospective, single-arm observational study conducted at two hospitals in Denmark. It is designed to assess how the SiA® System impacts inhaler technique and medication adherence over a 12-month period.

Key Features of the Study Design:

• Observational (non-interventional): Participants will continue their standard asthma medication (Trimbow pMDI) but will use the SiA® system to monitor their inhaler technique and adherence.
• Single-arm design: All participants will receive the SiA® System - there is no comparison group.
• Real-world setting: The study aims to reflect how patients interact with the SiA® system in everyday life, outside of a controlled clinical trial environment.

Study Setting:

• Conducted at two specialized respiratory clinics in Denmark.
• Participants will be recruited from routine asthma care visits.

Data Collection Methods:

Data will be collected through multiple sources:

• Hospital medical records (to gather historical asthma data and prior exacerbation history).
• Spirometry tests (to assess lung function).
• FeNO tests (to measure airway inflammation).
• SiA® System data (to track inhaler adherence and technique).
• Patient-reported outcome measures (questionnaires on asthma symptoms and quality of life).

Technology Used in the Study:

• RespiPRO™ Smart Inhaler Cap: A device that attaches to Trimbow pMDI and records inhaler usage data.
• SiA® Mobile App: Tracks daily inhaler use, provides feedback, and sends adherence reminders.

Study Timeline:

Total Study Duration: 22 months, with individual patient follow-up lasting 12 months (52 weeks).

Patient Flow and Study Visits:

1. Screening and Baseline Visit (Week 0) - Study Enrolment

   • Patients will be identified during routine asthma care visits and screened for eligibility.
   • Informed consent will be obtained.
   • Baseline data collection will include:
   • Medical history
   • Asthma severity and medication use
   • Spirometry test (lung function)
   • FeNO test (airway inflammation)
   • ACT (Asthma Control Test) and mini-AQLQ (Asthma Quality of Life Questionnaire)
   • Patients will receive a brief training session on how to use the SiA® System.
   • A baseline inhaler technique video will be recorded using the SiA® Mobile App.

2. Interim Follow-up Visit (Week 12) - Progress Check

   • Patients will return for an in-person visit.

   • Repeat measurements:

     • FeNO test (to check inflammation levels).
     • Spirometry (lung function test).
     • ACT and mini-AQLQ (patient-reported outcomes).

   • Adherence data from the SiA® system will be reviewed.

   • Patients will complete a satisfaction survey about their experience with the SiA® system.

3. Final Study Visit (Week 52) - End of Study

   • Repeat FeNO, spirometry, ACT, and mini-AQLQ assessments.
   • The final inhaler technique video will be recorded and analyzed.
   • Patients will return or deactivate the RespiPRO™ Smart Inhaler Cap.
   • Final adherence and inhalation technique data will be collected from the SiA® Dashboard.

Potential Impact of the Study

This study aims to generate real-world evidence on how digital health interventions can improve asthma management. If successful, the SiA® System could:

• Enhance asthma control by ensuring patients use their inhalers correctly.
• Reduce unnecessary medication escalation, preventing overuse of corticosteroids.
• Lower healthcare costs by reducing asthma-related hospital visits.
• Empower patients with real-time feedback and better self-management tools.
• Improve and optimize the way asthma patients become candidate for biological treatments

Inclusion Criteria:

1. Patients ≥18 years of age.

2. Objectively verified leading diagnosis of asthma according to GINA

3. FeNO >25 ppb.

4. Treated with Trimbow 87/5/9 pMDI for >4 weeks before enrolment,

   1. with prescribed rescue medication (SABA).
   2. with and without prescription of a spacer.

5. Being literate Danish.

6. Having a personal Android/iOS phone and 4G/5G internet connection.

7. Comfortable using a smart phone and Bluetooth enabled Digital Devices.

8. Willingness to participate in the study, understand the written patient information and being able to provide written informed consent.

Exclusion Criteria:

1. Participation in a clinical trial within 4 weeks prior to enrolment into the present study or planned enrolment in a clinical trial during the observational period.
2. Use of systemic corticosteroid as maintenance treatment.
3. Treated with biologics (that is monoclonal antibodies).
4. Concomitant diagnosis of COPD.
5. Lung cancer or history of lung cancer.
6. Respiratory tract infection/exacerbation within 4 weeks prior to enrolment.
7. Use of oral corticosteroids within 4 weeks before enrolment.