JMIR Publications

ABSTRACT

Background:

Patients with pulmonary arterial hypertension (PAH) – a progressive, ultimately fatal disease – often experience dyspnea which can limit their daily physical activities. Iloprost is an inhaled therapy for PAH that has shown efficacy in clinical trials. However, clinical trials in PAH have provided only limited data on parameters reflecting daily physical activity. Digital monitoring of daily physical activity in PAH is therefore attracting growing interest. To fully understand a patient’s response to treatment, monitoring of treatment adherence is also required. The Breelib™ nebulizer for administration of iloprost saves inhalation data, thus allowing digital monitoring of adherence.

Objective:

We aim to perform parallel digital tracking of daily physical activity parameters, heart rate, and iloprost inhalation data in patients with PAH before and after starting treatment with inhaled iloprost. The primary objective is to investigate correlations between changes in digital daily physical activity and traditional clinical measures. Secondary objectives are to assess iloprost inhalation behavior, the association between daily physical activity measures and time since last inhalation, changes in sleep quality and heart rate, the association of heart rate with daily physical activity measures and iloprost inhalation, and adverse events.

Methods:

VENTASTEP is a digital, prospective, observational, multicenter, single-arm cohort study of adults with PAH in Germany starting inhaled iloprost treatment via the Breelib™ nebulizer on top of existing PAH therapy. The study comprises a baseline period without iloprost treatment (≤ 2 weeks) and an observation period with iloprost treatment (3 months ± 2 weeks). The Apple Watch 2 and iPhone 6S are used with a dedicated study app to measure digital daily physical activity parameters and heart rate continuously during the baseline and observation periods; the watch is also used with a 6-minute walking distance (6MWD) app to measure digital 6MWD at baseline and the end-of-observation visit. Inhalation frequency, completeness, and duration are monitored digitally via the nebulizer and the BreeConnect™ app. Sleep quality is assessed using the Pittsburgh Sleep Quality Index at baseline and the end-of-observation visit. Changes in traditional outcome measures (6MWD, Borg dyspnea scale, EuroQol 5-dimensions questionnaire, functional class, and brain natriuretic peptide [BNP]/N-terminal pro-BNP) between baseline and the end-of-observation visit will be correlated with changes in digital daily physical activity parameters and digital 6MWD as the primary analysis.

Results:

The first participant was enrolled in February 2018 (estimated study completion: July 2019; planned sample size: 80 patients).

Conclusions:

The VENTASTEP study will provide a wealth of data to inform future research on the utility of digital parameters as outcome assessment tools for disease monitoring and guidance of treatment in PAH. The study will also provide insight into clinical outcomes, daily physical activity, and quality of life in patients starting inhaled iloprost on top of existing PAH therapy. Clinical Trial: ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407 (Archived by WebCite at http://www.webcitation.org/6ywPGcn4I)