An international, non-drug interventional, real-world cohort of PAH patients newly initiating PAH therapy with guideline-directed assessments of disease severity

Pulmonary arterial hypertension (PAH) is a serious chronic disorder of the
cardiopulmonary circulation, of diverse etiology and pathogenesis,
characterized by a progressive increase in pulmonary arterial pressure and
pulmonary vascular resistance affecting right heart function and potentially
leading to right heart failure and death (Benza 2010; Kylhammar 2014; Oudiz
2013). Estimated 1-, 3- and 5 year survival rates are 85% to 86%, 68% to 73%,
and 57% to 65%, respectively (Benza 2012a; Korsholm 2015; Radegran 2016).
The available therapies have positive effects on PAH, but the disease will
progress in many patients. Thus, PAH remains a serious life-threatening
condition, and research continues for better therapies.
Following results of the AMBITION trial (Galiè 2015) and various registry
analyses (REVEAL [Benza 2019a], SPAHR [Kylhammar 2018], COMPERA [Hoeper 2017],
FPHN [Boucly 2017]), based on the risk category for 1-year mortality defined in
the 2015 European Society of Cardiology (ESC) and the European Respiratory
Society (ERS) guidelines, current PAH treatment recommendations (Galiè 2019)
advocate the use of combined PAH therapies for an improved outcome for the
majority of patients.

Research Question
This study is designed to describe PAH patients in terms of their clinical
characteristics, therapies used, disease progression, and outcomes (eg, death,
hospitalization, risk category for predicted mortality risk [Boucly 2017; Benza
2019a; Benza 2020], and patient-reported outcomes [PROs]) in real-world
clinical practice. This study will collect high-quality real-world data that
may be used as a stand-alone dataset or in combination with other data sources
to address relevant research questions (eg, serve as an external control
dataset to another study) to support development and access to PAH therapies,
as well as to contribute to the knowledge base of PAH through publications.

This is a prospective, non-drug interventional, international, multicenter
study to collect real-world data from participants in a routine clinical
setting who newly initiate any PAH therapy(ies) in a real-world clinical
setting, either as first therapies, as replacement therapies, or as additional
therapies, or have already been receiving macitentan 10 mg for at least 3
months prior to index date. The index date is defined as the date when
participants starts the first new PAH therapy after baseline assessments have
been completed. Certain clinical visits and noninvasive assessments recommended
in the 2015 ESC/ERS guidelines are mandated in this study to ensure
availability of data to address the study objectives (Galiè 2016).
The decision of patients to participate in this study must not, in any way,
impact upon the standard of care that they are receiving or any benefits to
which they are otherwise entitled. The treatment decision must have been taken
prior to and independently of the participant's inclusion in the study. All
aspects of treatment and clinical management of participants will be in
accordance with local clinical practice and applicable local regulations, and
at the discretion of the participating physician (or treating physician where
different).
The study population will consist of consenting participants who have newly
initiated a PAH therapy since the beginning of the enrollment period in
participating centers, clinics, or healthcare facilities. All participants
qualifying to the enrollment plan (designed based on PAH therapy initiated at
index date, geographic location, site type, background PAH therapy, etc) and
fulfilling all the inclusion criteria and none of the exclusion criteria will
be enrolled in the study and be observed in the study until end of study,
withdrawal of informed consent, loss to follow-up, or death.
All participants must sign an informed consent form (ICF) on the same day or
before any data collection and source data verification in accordance with
local requirements and/or sponsor policy.
To ensure data quality, certain follow-up visits and noninvasive assessments
recommended in the 2015 ESC/ERS guidelines (Galiè 2016) will be mandated in
this study. In addition, participants will be followed by their physician
according to routine clinical practice and as permitted by local regulation.
Furthermore, study sites will have quarterly telephone contacts with
participants to capture data related to occurrence of clinical events, safety
events, and changes in PAH and/or concomitant medications. Aside from the
mandated visits, participants will be followed by their physician as needed.
The end of the study will be the last data point collection for the last
participant. The overall duration of the study may be up to 6 years; however,
this non-drug interventional study may be discontinued at any time by the
sponsor at the sponsor's discretion.

The burden and risks of only the study assessments (blood sampling and
completing questionnaires) are low. Completing the questionnaires takes
approximately 15 to 20 minutes in total. 2.5 ml of blood is taken per blood
sample (8 times in total)
The study assessments are carried out during the visits that are already taking
place as part of the standard treatment.