AsthmaOUTERSPACE-3NCT06360393
Inhaler Adherence and Inhalation Technique Assessed by a Smart Spacer in Patients with Severe Asthma on Biologics
An observational study of Asthma, run by University Medical Center Groningen at 5 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Asthma
- What is being tested?
- Smart spacer
- Type of treatment
- Medical device
- How many people
- 110 participants
- Where
- 5 sitesNetherlands
- Study dates
- 1 May 2024to Jun 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites, 5 recruiting
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 9713GZ
Maarten van den Berge, MD, PhD, +31 6 24450194, m.van.den.berge@umcg.nl
Titia Klemmeier, RN
- Recruiting
Foundation Martini Hospital
Groningen, Provincie Groningen, 9728NT
Marjolein J van Es, MD, PhD, +31 50 524 5245, m.vanes@mzh.nl
- Recruiting
Medisch Centrum Leeuwarden
Leeuwarden, Provincie Friesland, 8934AD
Akke-Nynke van der Meer, MD, PhD, +31 58 286 3875, a.n.van.der.meer@mcl.nl
- Recruiting
Stichting Sint Franciscus Vlietland Groep
Rotterdam, South Holland, 3118JH
Yasemin Türk, MD, PhD, +31 10 461 6161, yasemin.turk@Franciscus.nl
- Recruiting
Isala
Zwolle, Overijssel, 8025AB
Niels Patberg, MD, k.w.patberg@isala.nl
About this study
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:
Read more
- 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.
- 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.
- 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.
Read the 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:
- 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.
- 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.
- 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.
- Conditions
- Asthma
- Being tested
- Smart spacer
- Keywords
- Severe asthma, Biologics, Digital home monitoring, Digital spacer, Adherence, Inhalation technique
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Smart spacerDevice
Participants' inhalation medication adherence and inhalation technique will be monitored using a smart spacer. Their usual medication regime will be continued and they will not receive information about their adherence or inhalation technique measured by the spacer during the follow-up year (except for any interventions that will be done in standard care).
| Study group | Role | What they receive |
|---|---|---|
| Severe asthma patients on biologics | Participants diagnosed with severe asthma using a biologic medication and medium or high dose ICS + LABA with or without LAMA and/or SABA via pMDI and spacer. Participants are being treated at one of the five severe asthma clinics in The Netherlands. Receives: Device: Smart spacer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparative analysis of smart spacer medication adherence and inhaler technique against Test of Adherence to Inhalers (TAI-12)
An evaluation of the inhalation adherence patterns and inhaler techniques of patients utilizing smart spacer devices in comparison to traditional inhaler usage assessed by the Test of Adherence to Inhalers (TAI-12).
TAI is a questionnaire which identifies patients with low adherence, determines the degree of adherence and gives an idea of the type or pattern of non-compliance. The TAI-12 consists of 10 questions for the patient and 2 questions for the healthcare provider and identifies patients with poor adherence and their degree of adherence. The scoring for the patient part is: for each question ranges from 1 to 5 (1 = worst compliance to 5 = best compliance). All items provide a total score of between 10 (minimum) and 50 (maximum). A higher score is related to better adherence. The scoring of the healthcare provider part is: a minimum of 2 points and a maximum of 4 points. A higher score also relates to a better adherence.
Measured: TAI is measured at baseline and 12 months
Comparison of smart spacer medication adherence patterns (adherence and inhaler technique) with inhaler checklist examined by pulmonologist or pulmonary nurse
An evaluation of the inhalation adherence patterns and inhaler techniques of patients utilizing smart spacer devices in comparison to traditional inhaler usage assessment by healthcare professionals using an inhalation technique checklist.
The inhalation technique checklist is created by following the national inhalation technique guidelines by the Lung Foundation in The Netherlands (Long Alliantie Nederland, LAN), specifically for using a pMDI in combination with a spacer. The checklist consists of 8 points to assess the inhalation technique on (from the preparation of the device, to the positioning of the device and posture of the patient, and the actual inhalation).
Measured: Inhaler checklist is assessed at baseline and 12 months
Secondary outcomes (7)
Assessing the association of smart spacer assessed adherence with annual exacerbation rate
An assessment of the association between inhalation medication adherence measured by smart spacer devices and the annual exacerbation rate.
The annual exacerbation rate will include the number of exacerbations of the participant in the one-year follow-up and the severity of the exacerbation (e.g. increased reliever use, oral corticosteroid use, emergency room visit, hospitalization).
Measured: Over a period of 12 months
Assessing the association of smart spacer assessed adherence with reliever inhaler use (e.g. SABA)
An examination of the possible association between inhalation medication adherence measured by smart spacer devices and the use of reliever medication.
The use of reliever medication will also be monitored by the smart spacer and it is included as a question in the Asthma Control Questionnaire (question 6).
Measured: Over a period of 12 months
Assess the association of smart spacer assessed adherence with oral corticosteroids use
An examination of the possible association between inhalation medication adherence measured through smart spacer devices and the use of oral corticosteroids (OCS).
The use of OCS will be defined as total annual OCS exposure (in milligrams) as well as the number of high dose (> 30 milligrams) short courses (between 3 to 14 days).
Measured: Over a period of 12 months
Assess the association of smart spacer assessed adherence with FeNO results
An examination of the possible association between inhalation medication adherence measured through smart spacer devices and FeNO measurements.
Fractional exhaled nitric oxide (FeNO) serves as an indicator of inflammation in asthma. It has been employed as a measure to detect non-compliance with inhaled corticosteroid (ICS) therapy. Individuals who do not adhere to ICS treatment typically exhibit elevated FeNO levels since ICS effectively suppress FeNO. A high FeNO level despite ICS usage suggests ongoing inflammation in the airways due to asthma, increasing the likelihood of exacerbations. The difference in FeNO measured at baseline and 12 months will be compared the overall ICS adherence.
Measured: FeNO is measured at baseline and 12 months
Assess the association of smart spacer assessed adherence with blood eosinophils
An examination of the possible association between inhalation medication adherence measured through smart spacer devices and blood eosinophils.
Blood eosinophils are a type of white blood cell that plays a significant role in the immune response, particularly in allergic reactions and inflammatory conditions. Asthma is characterized by chronic inflammation of the airways, and eosinophils are one of the key inflammatory cells involved. Elevated levels of eosinophils in the blood can indicate ongoing inflammation in the airways. Blood eosinophil levels can also serve as a biomarker for predicting response to certain asthma treatments, particularly corticosteroids. Elevated blood eosinophil levels have been associated with an increased risk of asthma exacerbations. The difference in eosinophils measured at baseline and 12 months will be compared the overall ICS adherence.
Measured: Blood eosinophils measured at baseline and 12 months
Assess the association of smart spacer assessed adherence with asthma control (ACQ-6)
An examination of the possible association between adherence measured through smart spacer Asthma Control assessed with the Asthma Control Questionnaire (ACQ-6).
This questionnaire consists of six questions about the severity of symptoms which a patient experiences. The score range per question is 0 to 7 (0 = never and 7 = always). The total score will be calculated by dividing the sum of all scores by the amount of questions. A higher score is associated with worse asthma control. The difference in ACQ outcomes at baseline, 6-months and 12 months will be compared the overall ICS adherence.
Measured: ACQ is measured at baseline, 6 months and 12 months
Assess the association of smart spacer assessed adherence with spirometry results
An examination of the possible association between adherence measured through smart spacer devices and spirometry results.
Spirometry is a pulmonary function test that measures how much air a person can inhale and exhale, as well as how quickly they can exhale. Asthma often shows a reduced forced expiratory volume in one second (FEV1) and a reduced FEV1 to forced vital capacity (FVC) ratio, indicating obstruction. Lower spirometry readings, particularly a lower FEV1, may indicate poorly controlled asthma, which is associated with an increased risk of exacerbations. Measured: Forced Vital Capacity (FVC) (% pred), Forced Expiratory Volume in one second (FEV1) (% pred), Peak Expiratory Flow (PEF) (L/min), and FEV1/FVC ratio. The difference in spirometry results at baseline and 12 months will be compared the overall ICS adherence.
Measured: Spirometry is performed at baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2024
- Study start1 May 2024
- Primary completionMar 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Trudell Medical International
- Responsible party
- Sponsor
- Investigators
- Job FM van Boven, PharmD, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06360393
- Sponsor's protocol ID
- 17384
- Acronym
- OUTERSPACE-3
- Status last verified
- Apr 2024
- First submitted
- 8 Apr 2024
- Last updated
- 10 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015 Apr;135(4):896-902. doi: 10.1016/j.jaci.2014.08.042. Epub 2014 Oct 16.
PubMed 25441637McQueen RB, Sheehan DN, Whittington MD, van Boven JFM, Campbell JD. Cost-Effectiveness of Biological Asthma Treatments: A Systematic Review and Recommendations for Future Economic Evaluations. Pharmacoeconomics. 2018 Aug;36(8):957-971. doi: 10.1007/s40273-018-0658-x.
PubMed 29736895Barry LE, Sweeney J, O'Neill C, Price D, Heaney LG. The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis. Respir Res. 2017 Jun 26;18(1):129. doi: 10.1186/s12931-017-0614-x.
PubMed 28651591Hale EM, Greene G, Mulvey C, Mokoka MC, van Boven JFM, Cushen B, Sulaiman I, Brennan V, Lombard L, Walsh J, Plunkett S, McCartan TA, Kerr PJ, Reilly RB, Hughes C, Kent BD, Jackson DJ, Butler M, Counihan I, Hayes J, Faul J, Kelly M, Convery R, Nanzer AM, Fitzgerald JM, Murphy DM, Heaney LG, Costello RW; INCA Research Team. Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial. Lancet Respir Med. 2023 Jul;11(7):591-601. doi: 10.1016/S2213-2600(22)00534-3. Epub 2023 Mar 21.
PubMed 36963417d'Ancona G, Kavanagh J, Roxas C, Green L, Fernandes M, Thomson L, Dhariwal J, Nanzer AM, Jackson DJ, Kent BD. Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma. Eur Respir J. 2020 May 7;55(5):1902259. doi: 10.1183/13993003.02259-2019. Print 2020 May.
PubMed 32060061d'Ancona G, Kavanagh JE, Dhariwal J, Hearn AP, Roxas C, Fernandes M, Green L, Thomson L, Nanzer AM, Jackson DJ, Kent BD. Adherence to inhaled corticosteroids and clinical outcomes following a year of benralizumab therapy for severe eosinophilic asthma. Allergy. 2021 Jul;76(7):2238-2241. doi: 10.1111/all.14737. Epub 2021 Jan 26. No abstract available.
PubMed 33432682Dekhuijzen R, Lavorini F, Usmani OS, van Boven JFM. Addressing the Impact and Unmet Needs of Nonadherence in Asthma and Chronic Obstructive Pulmonary Disease: Where Do We Go From Here? J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):785-793. doi: 10.1016/j.jaip.2017.11.027. Epub 2018 Jan 12.
PubMed 29339126van Boven JF, Ryan D, Eakin MN, Canonica GW, Barot A, Foster JM; Respiratory Effectiveness Group. Enhancing Respiratory Medication Adherence: The Role of Health Care Professionals and Cost-Effectiveness Considerations. J Allergy Clin Immunol Pract. 2016 Sep-Oct;4(5):835-46. doi: 10.1016/j.jaip.2016.03.007.
PubMed 27587317O'Dwyer S, Greene G, MacHale E, Cushen B, Sulaiman I, Boland F, Bosnic-Anticevich S, Mokoka MC, Reilly RB, Taylor T, Ryder SA, Costello RW. Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial. J Allergy Clin Immunol Pract. 2020 Feb;8(2):635-644. doi: 10.1016/j.jaip.2019.09.008. Epub 2019 Sep 27.
PubMed 31568927Jansen EM, van de Hei SJ, Dierick BJH, Kerstjens HAM, Kocks JWH, van Boven JFM. Global burden of medication non-adherence in chronic obstructive pulmonary disease (COPD) and asthma: a narrative review of the clinical and economic case for smart inhalers. J Thorac Dis. 2021 Jun;13(6):3846-3864. doi: 10.21037/jtd-20-2360.
PubMed 34277075Vincken W, Levy ML, Scullion J, Usmani OS, Dekhuijzen PNR, Corrigan CJ. Spacer devices for inhaled therapy: why use them, and how? ERJ Open Res. 2018 Jun 18;4(2):00065-2018. doi: 10.1183/23120541.00065-2018. eCollection 2018 Apr.
PubMed 29928649Price DB, Roman-Rodriguez M, McQueen RB, Bosnic-Anticevich S, Carter V, Gruffydd-Jones K, Haughney J, Henrichsen S, Hutton C, Infantino A, Lavorini F, Law LM, Lisspers K, Papi A, Ryan D, Stallberg B, van der Molen T, Chrystyn H. Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):1071-1081.e9. doi: 10.1016/j.jaip.2017.01.004. Epub 2017 Mar 9.
PubMed 28286157Normansell R, Kew KM, Mathioudakis AG. Interventions to improve inhaler technique for people with asthma. Cochrane Database Syst Rev. 2017 Mar 13;3(3):CD012286. doi: 10.1002/14651858.CD012286.pub2.
PubMed 28288272Dierick BHJ, Achterbosch M, Been-Buck S, Klemmeier T, van de Hei SJ, Hagedoorn P, Kerstjens HAM, Kocks JWH, van Boven JFM. Can electronic monitoring with a digital smart spacer support personalised medication adherence and inhaler technique education in patients with asthma?: Protocol of the randomised controlled OUTERSPACE trial. BMJ Open. 2022 Jun 13;12(6):e059929. doi: 10.1136/bmjopen-2021-059929.
PubMed 35697450Dierick BJH, Been-Buck S, Klemmeier T, Hagedoorn P, van de Hei SJ, Kerstjens HAM, Kocks JWH, Zijp TR, Wessels AMA, Touw DJ, van Boven JFM. Digital spacer data driven COPD inhaler adherence education: The OUTERSPACE proof-of-concept study. Respir Med. 2022 Sep;201:106940. doi: 10.1016/j.rmed.2022.106940. Epub 2022 Jul 31.
PubMed 35933835
Study at a glance
From the registry record, last updated by the sponsor on 10 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaler Adherence and Inhalation Technique Assessed by a Smart Spacer in Patients with Severe Asthma on Biologics
- ClinicalTrials.gov ID
- NCT06360393
- Acronym / sponsor ID
- OUTERSPACE-3 / 17384
- Conditions
- Asthma
- Keywords
- Severe asthma, Biologics, Digital home monitoring, Digital spacer, Adherence, Inhalation technique
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Trudell Medical International
- Study start
- 1 May 2024 (actual)
- Primary completion
- Mar 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 11 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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:
- 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.
- 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.
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Severe asthma patients on biologics | – | Device: Smart spacerParticipants diagnosed with severe asthma using a biologic medication and medium or high dose ICS + LABA with or without LAMA and/or SABA via pMDI and spacer. Participants are being treated at one of the five severe asthma clinics in The Netherlands. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Smart spacerParticipants' inhalation medication adherence and inhalation technique will be monitored using a smart spacer. Their usual medication regime will be continued and they will not receive information about their adherence or inhalation technique measured by the spacer during the follow-up year (except for any interventions that will be done in standard care). | Device | Severe asthma patients on biologics |
Primary outcome
Comparative analysis of smart spacer medication adherence and inhaler technique against Test of Adherence to Inhalers (TAI-12)
Time frame: TAI is measured at baseline and 12 months
An evaluation of the inhalation adherence patterns and inhaler techniques of patients utilizing smart spacer devices in comparison to traditional inhaler usage assessed by the Test of Adherence to Inhalers (TAI-12). TAI is a questionnaire which identifies patients with low adherence, determines the degree of adherence and gives an idea of the type or pattern of non-compliance. The TAI-12 consists of 10 questions for the patient and 2 questions for the healthcare provider and identifies patients with poor adherence and their degree of adherence. The scoring for the patient part is: for each question ranges from 1 to 5 (1 = worst compliance to 5 = best compliance). All items provide a total score of between 10 (minimum) and 50 (maximum). A higher score is related to better adherence. The scoring of the healthcare provider part is: a minimum of 2 points and a maximum of 4 points. A higher score also relates to a better adherence.
Comparison of smart spacer medication adherence patterns (adherence and inhaler technique) with inhaler checklist examined by pulmonologist or pulmonary nurse
Time frame: Inhaler checklist is assessed at baseline and 12 months
An evaluation of the inhalation adherence patterns and inhaler techniques of patients utilizing smart spacer devices in comparison to traditional inhaler usage assessment by healthcare professionals using an inhalation technique checklist. The inhalation technique checklist is created by following the national inhalation technique guidelines by the Lung Foundation in The Netherlands (Long Alliantie Nederland, LAN), specifically for using a pMDI in combination with a spacer. The checklist consists of 8 points to assess the inhalation technique on (from the preparation of the device, to the positioning of the device and posture of the patient, and the actual inhalation).
7 secondary outcomes
Assessing the association of smart spacer assessed adherence with annual exacerbation rate
Time frame: Over a period of 12 months
Assessing the association of smart spacer assessed adherence with reliever inhaler use (e.g. SABA)
Time frame: Over a period of 12 months
Assess the association of smart spacer assessed adherence with oral corticosteroids use
Time frame: Over a period of 12 months
Assess the association of smart spacer assessed adherence with FeNO results
Time frame: FeNO is measured at baseline and 12 months
Assess the association of smart spacer assessed adherence with blood eosinophils
Time frame: Blood eosinophils measured at baseline and 12 months
Assess the association of smart spacer assessed adherence with asthma control (ACQ-6)
Time frame: ACQ is measured at baseline, 6 months and 12 months
Assess the association of smart spacer assessed adherence with spirometry results
Time frame: Spirometry is performed at baseline and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Dec 2024.
- Background: PubMed 25441637Hekking PW, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015 Apr;135(4):896-902. doi: 10.1016/j.jaci.2014.08.042. Epub 2014 Oct 16.
- Background: PubMed 29736895McQueen RB, Sheehan DN, Whittington MD, van Boven JFM, Campbell JD. Cost-Effectiveness of Biological Asthma Treatments: A Systematic Review and Recommendations for Future Economic Evaluations. Pharmacoeconomics. 2018 Aug;36(8):957-971. doi: 10.1007/s40273-018-0658-x.
- Background: PubMed 28651591Barry LE, Sweeney J, O'Neill C, Price D, Heaney LG. The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis. Respir Res. 2017 Jun 26;18(1):129. doi: 10.1186/s12931-017-0614-x.
- Background: PubMed 36963417Hale EM, Greene G, Mulvey C, Mokoka MC, van Boven JFM, Cushen B, Sulaiman I, Brennan V, Lombard L, Walsh J, Plunkett S, McCartan TA, Kerr PJ, Reilly RB, Hughes C, Kent BD, Jackson DJ, Butler M, Counihan I, Hayes J, Faul J, Kelly M, Convery R, Nanzer AM, Fitzgerald JM, Murphy DM, Heaney LG, Costello RW; INCA Research Team. Use of digital measurement of medication adherence and lung function to guide the management of uncontrolled asthma (INCA Sun): a multicentre, single-blinded, randomised clinical trial. Lancet Respir Med. 2023 Jul;11(7):591-601. doi: 10.1016/S2213-2600(22)00534-3. Epub 2023 Mar 21.
- Background: PubMed 32060061d'Ancona G, Kavanagh J, Roxas C, Green L, Fernandes M, Thomson L, Dhariwal J, Nanzer AM, Jackson DJ, Kent BD. Adherence to corticosteroids and clinical outcomes in mepolizumab therapy for severe asthma. Eur Respir J. 2020 May 7;55(5):1902259. doi: 10.1183/13993003.02259-2019. Print 2020 May.
- Background: PubMed 33432682d'Ancona G, Kavanagh JE, Dhariwal J, Hearn AP, Roxas C, Fernandes M, Green L, Thomson L, Nanzer AM, Jackson DJ, Kent BD. Adherence to inhaled corticosteroids and clinical outcomes following a year of benralizumab therapy for severe eosinophilic asthma. Allergy. 2021 Jul;76(7):2238-2241. doi: 10.1111/all.14737. Epub 2021 Jan 26. No abstract available.
- Background: PubMed 29339126Dekhuijzen R, Lavorini F, Usmani OS, van Boven JFM. Addressing the Impact and Unmet Needs of Nonadherence in Asthma and Chronic Obstructive Pulmonary Disease: Where Do We Go From Here? J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):785-793. doi: 10.1016/j.jaip.2017.11.027. Epub 2018 Jan 12.
- Background: PubMed 27587317van Boven JF, Ryan D, Eakin MN, Canonica GW, Barot A, Foster JM; Respiratory Effectiveness Group. Enhancing Respiratory Medication Adherence: The Role of Health Care Professionals and Cost-Effectiveness Considerations. J Allergy Clin Immunol Pract. 2016 Sep-Oct;4(5):835-46. doi: 10.1016/j.jaip.2016.03.007.
- Background: PubMed 31568927O'Dwyer S, Greene G, MacHale E, Cushen B, Sulaiman I, Boland F, Bosnic-Anticevich S, Mokoka MC, Reilly RB, Taylor T, Ryder SA, Costello RW. Personalized Biofeedback on Inhaler Adherence and Technique by Community Pharmacists: A Cluster Randomized Clinical Trial. J Allergy Clin Immunol Pract. 2020 Feb;8(2):635-644. doi: 10.1016/j.jaip.2019.09.008. Epub 2019 Sep 27.
- Background: PubMed 34277075Jansen EM, van de Hei SJ, Dierick BJH, Kerstjens HAM, Kocks JWH, van Boven JFM. Global burden of medication non-adherence in chronic obstructive pulmonary disease (COPD) and asthma: a narrative review of the clinical and economic case for smart inhalers. J Thorac Dis. 2021 Jun;13(6):3846-3864. doi: 10.21037/jtd-20-2360.
- Background: PubMed 29928649Vincken W, Levy ML, Scullion J, Usmani OS, Dekhuijzen PNR, Corrigan CJ. Spacer devices for inhaled therapy: why use them, and how? ERJ Open Res. 2018 Jun 18;4(2):00065-2018. doi: 10.1183/23120541.00065-2018. eCollection 2018 Apr.
- Background: PubMed 28286157Price DB, Roman-Rodriguez M, McQueen RB, Bosnic-Anticevich S, Carter V, Gruffydd-Jones K, Haughney J, Henrichsen S, Hutton C, Infantino A, Lavorini F, Law LM, Lisspers K, Papi A, Ryan D, Stallberg B, van der Molen T, Chrystyn H. Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes. J Allergy Clin Immunol Pract. 2017 Jul-Aug;5(4):1071-1081.e9. doi: 10.1016/j.jaip.2017.01.004. Epub 2017 Mar 9.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Job FM van Boven, PharmD, PhD principal investigator
University Medical Center Groningen
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma, run by University Medical Center Groningen at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Job FM van Boven, PharmD, PhD (+31 50 361 7893, j.f.m.van.boven@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparative analysis of smart spacer medication adherence and inhaler technique against Test of Adherence to Inhalers (TAI-12) (time frame: TAI is measured at baseline and 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06360393, which also lists 16 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2024.