OUTER SPACE-2: a randomised study on inhaler treatment adherence using a smart spacer in adults with asthma

In the Netherlands, around 586,200 people have asthma.1,2 Globally, asthma is
a main cause of disability, health care services utilization, and quality of
life impairment.3,4 Asthma management aims to achieve good symptom control,
minimize exacerbations, reduce side effects and as a result prevent the
progression of obstructive lung damage.5
Although the majority of asthma patients can be effectively controlled with the
available medications, a substantial subset remains uncontrolled despite being
offered the optimal therapy.5,6 Poor adherence to treatment is one of the
commonest causes of poor control and is widely reported in patients with all
severit ies of asthma.7,8 Achieving adherence can significantly reduce the
disease burden. Yet, the key challenge that physicians, pharmacists and nurses
are facing is helping patients with asthma finding a way to ensure good
adherence.9 Whilst elements of adherence, such as moment of inhalation, have
been studied10, studies of adherence to treatment between clinic visits
including the vital domain of how devices are used are limited.11
Effective treatment of many respiratory illnesses requires drug delivery to the
airways and lungs. The devices which are used to achieve this include
nebulisers, dry powder inhalers (DPIs) and pressurised metered dose inhalers
(pMDIs). The latter are most commonly used in combination with spacers (or
valved holding chambers) as recommended in the Dutch primary care NHG
guidelines. There are several reasons behind the preference for pMDI and spacer
use12, including: (i) they are usually the cheapest option, (ii) DPIs are
unsuitable for people that cannot generate sufficient inspiratory flow.
However, many patients persist with critical errors in inhaler technique,
leading to poorer disease control and poorer outcomes.13 A Cochrane Review of
interventions to improve inhaler technique for people with asthma in 2017
concluded that *Guidelines consistently recommend that clinicians check
regularly the inhaler technique of their patients; what is not clear is how
clinicians can most effectively intervene if they find a patient*s technique to
be inadequate, and whether such interventions will have a discernible impact on
clinical outcomes*.14
Complete adherence for inhaled medications has two components: i.
*implementation and persistence* and ii. inhaler technique.15 Implementation
and persistence in this context is intended to describe the extent to which an
individual uses the medication at the directed times for a chronic period. This
can be measured using patient diaries, which are prone to reporting error or
more accurately using electronic inhaler monitors. Studies with these devices
show that persistence with treatment is relatively poor in most settings but
this may be improved by educational interventions. A recent UK study showed
that average persistence for children with asthma was 49% for those who were
monitored but received no reminders and 70% for those who received reminders to
take their treatment.16 However, while the number of puffs taken improved,
asthma control did not improve, likely due to lack of inhaler technique
improvement. Whilst inhaler technique is regularly checked, in mostly primary
care clinic visits, this aspect of adherence is much more difficult to monitor
remotely.
Most patients with asthma use spacers in combination with pMDIs to assist
optimal drug delivery to the lungs. Until recently their use has been difficult
to measure. Understanding if critical errors in administration of inhaled
medications are occurring is vital if healthcare professionals are to be able
to effectively educate people with asthma.
We aim to assess the feasibility - and explore the effects - of tailored
inhaler education by a GP/nurse supported by a CE-marked smart spacer that
monitors adherence and inhaler technique, and compare this with usual, generic
primary care based asthma management.

Primary objective:
To assess the overall feasibility of undertaking a definitive randomized
controlled trial on the effects of tailored inhaler education by the GP/nurse
supported by a smart spacer, in primary care treated adults with asthma.

Secondary objectives:
1) determine patient recruitment speed, participation rate (proportion of
eligible patients), drop-out rate and inform sample size calculation for a
definitive trial.
2) assess patient and healthcare provider satisfaction with the workflow
(System Usability Scale [SUS]).
3) explore the distribution of medication adherence patterns (persistence and
inhaler technique) and clinical outcomes (lung function, FeNO, Asthma Control
Questionnaire [ACQ], Test for Adherence to Inhalers [TAI], and Work
Productivity and Activity Impairment questionnaire [WPAI], SABA use, oral
steroid bursts)

Single center, randomized controlled feasibility trial of 2 months. Patients
will be recruited from 4 GP practices in the Netherlands. Patients (n=40) will
use the smarts spacer for 1 month (t=-1). Then they will be randomized in two
groups (t=0). The control group will get usual care, the intervention group
will get tailored feedback and education on basis of data from the smart
spacer. After 1 month (t=1) the study is ended and patients will get again
their usual care.
At t=-1. t=0 and t=1 ACQ, WPAI an TAI questionnaires and FeNO test will be
assessed. At t=0 and t=1 a lung function will be tested. At t=1 usability will
be analyzed by the SUS questionnaire and structured interviews with 5 patients
and all caregivers.

The investigational treatment is tailored inhaler use education, supported by
data generated by a smart spacer. In addition to usual care, patients in the
intervention group receive detailed information about how and when they used
their inhaled medications. If errors in medication use are identified,
protocolled education by the GP/nurse in line with Dutch guidelines will be
provided to help eliminate errors. To overcome inter-nurse bias, and to
protocolize the education, the nurses are instructed to use the *TAI Toolkit*.
11

The burden and risks associated with participation in this study is very
limited. Patients will receive usual care until the intervention. The
intervention is tailoring the education. The education itself is usual care,
only the choice which education is given is smart spacer data driven. Patients
may experience extra burden due to the extra spirometry and the FeNO test,
furthermore patients are asked to fill in the questionnaires. The burden of
these tests and questionnaires is deemed limited.