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 study will also provide insight into clinical outcomes, daily physical activity, and quality of life in patients adding inhaled iloprost, to existing PAH therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03293407; https://clinicaltrials.gov/ct2/show/NCT03293407 (Archived by WebCite at http://www.webcitation.org/6ywPGcn4I). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12144.
ABSTRACT
Inhaled iloprost is an effective therapy for patients with pulmonary arterial hypertension (PAH); however, some patients experience extended inhalation times when using the V10 formulation (10.0 µg/mL) to deliver a 5 -µg dose (at mouthpiece) and are at risk of incomplete inhalations and reduced inhalation frequency. VENTASWITCH was an observational, case-crossover study to evaluate inhalation behavior in patients with PAH switched from iloprost V10 to V20 (20.0 µg/mL) formulation for delivering a 5 -µg dose using the I-Neb® AAD® device. Adults with PAH participating in a German Ventavis® (iloprost) patient-support program, who were switched from the V10 to V20 formulation, were enrolled. The co-primary endpoints were mean daily proportion of complete inhalations and mean daily inhalation frequency. The secondary endpoint was mean daily inhalation duration. Data were collected for three months before and after switching. Overall, 63 patients were included. Switching from V10 to V20 resulted in a significant increase in the mean daily proportion of complete inhalations (92% vs. 97%, P < 0.0001) and inhalation frequency (4.6 vs. 4.9 inhalations/day, P = 0.0430), and reduction in mean inhalation duration (11.8 vs. 6.5 min; P < 0.0001). Greater increases in daily proportions of complete inhalations were observed in older patients (≥ 65 vs. < 65 years) and those receiving more (3 vs. < 3) concomitant PAH medications. Switching from V10 to V20 iloprost formulation significantly improved inhalation behavior in patients with PAH and may facilitate improved adherence to therapy.
ABSTRACT
Little is known about the onset of action after intravenous or oral administration of acetylsalicylic acid (ASA) in patients with acute coronary syndromes (ACS). The aim of the study was to compare intravenous 250 or 500 mg acetylsalicylic acid (ASA) with oral 300 mg in ASA naïve patients with ACS concerning the onset of antiplatelet effects measured by time dependent thromboxane inhibition. A total of 270 patients with ACS < 24 hours were randomised into one of three treatment arms comprising administration of a single dose of ASA as soon as possible after admission. The primary endpoint was platelet inhibition assessed by measurement of arachidonic acid (AA)-induced platelet thromboxane release (TXB2) 5 minutes (min) after study drug administration. Both 250 mg and 500 mg ASA i. v. inhibited TXB2 formation nearly completely (geometric means: from 581.7 and 573.9 ng/ml at baseline to 3.9 and 3.1 ng/ml at 5 min, respectively) compared to 300 mg oral ASA (geometric means: from 652.0 to 223.7 ng/ml) (p-value, ANCOVA: < 0.0001). Similar results were obtained for inhibition of AA-induced platelet aggregation (Multiplate ASPItest; from means 86.41 and 85.72 U to 23.04 and 20.57 U at 5 min, respectively) compared to 300 mg oral ASA from mean 87.18 to 75.56 U (p-value, ANCOVA: <0.0001). The rate of bleedings was low and comparable between the groups. In summary, the administration of a single dose of 250 or 500 mg ASA IV compared to 300 mg orally is associated with a faster and more complete inhibition of thromboxane generation and platelet aggregation. Bleeding complications were comparable between the groups.
