Evaluation of Clinical Outcomes and Simultaneous Digital Tracking of Daily Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Protocol for the Observational VENTASTEP Study

Abstract

Background Pulmonary arterial hypertension (PAH)—a progressive, ultimately fatal disease—patients 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 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 This study aims to perform parallel digital tracking of daily physical activity parameters, heart rate, and iloprost inhalation data in patients with PAH, before and after starting inhaled iloprost treatment. The primary objective is to investigate correlations between changes in digital measures of 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, in addition to 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 Series 2 and iPhone 6s are used with a dedicated study app to continuously measure digital daily physical activity parameters and heart rate during the baseline and observation periods; the watch is also used with a 6-min walk 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] or N-terminal proBNP) 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 by July 2019; planned sample size: 80 patients). Conclusions The VENTASTEP study will inform future research on the utility of digital parameters as outcome assessment tools for disease monitoring in PAH. The st...

Digital Tracking of Physical Activity, Heart Rate, and Inhalation Behavior in Patients With Pulmonary Arterial Hypertension Treated With Inhaled Iloprost: Observational Study (VENTASTEP)

“…Recruitment was limited by a lack of available patients, which resulted in a small study population. This could be partly due to the rarity of pulmonary arterial hypertension [ 17 ], the willingness of patients to undergo digital monitoring, and the suitability of the study devices for the patients [ 14 ]. Nevertheless, data were fully available in the full analysis set for most outcome variables.…”

“…However, measurement of 6-minute walk distance by GPS or Wi-Fi would require precise location tracking. A feasibility survey suggested that precise tracking on a long-term basis would not be accepted by patients [ 14 ]; such tracking would, therefore, need to be restricted to during the 6-minute walk distance test (eg, by designing the 6-minute walk distance app to automatically switch GPS and Wi-Fi tracking on at the start of the 6-minute walk distance test and off at the end of the test).…”

“…In preparation for this study, a survey on acceptance of digital tracking was performed, which indicated that approximately 50% of patients were willing to participate [ 14 ].…”

Risk assessment in patients with pulmonary arterial hypertension in the era of COVID 19 pandemic and the telehealth revolution: State of the art review

“…AliveCor KardiaMobile) may serve this purpose ( Table 2). A study evaluating clinical outcomes using simultaneous digital tracking of daily physical activity, heart rate, and inhalation behavior in PAH patients treated with inhaled iloprost is underway 56 . This provocative study will provide insight into clinical outcomes, daily physical activity, and quality of life in patients with PAH and inform future research on wearable technology in this population.…”