Prospective, Non-interventional, Multi-center, Post-authorization Safety Study of Riociguat for Pulmonary Arterial Hypertension (PAH)

Study Overview
=================
Brief Summary
-----------------
The primary objective in this study is to collect post-marketing information on Riociguat safety.Thus, the information on adverse events (AEs) and adverse drug reactions (ADRs) that occur within the first 12 months and in the following 6 -year observation at most, after starting Riociguat treatment under the routine clinical practice will be collected. The secondary objectives are collecting information on Riociguat effectiveness, such as 6-Minute Walking Distance (6MWD) Test. Since it is assumed that Riociguat is for long-term use, information on Pulmonary Arterial Hypertension (PAH) clinical worsening will also be surveyed once a year.

Detailed Description
-----------------
This local, prospective, non-interventional, multi-center study includes patients treated with Riociguat for PAH. A total of 600 patients (valid for safety analysis) is planned to be included in 4 years. This study is performed as an all-case investigation therefore; all patients who receive Riociguat treatment for PAH need to be registered, in principle. The treatment should be performed based on the product label in Japan. The standard observation period will last for 12 months from starting Riociguat treatment. Safety and effectiveness will be evaluated at the 3rd and 12th month of treatment. In addition, the extension observation period will be carried out as long as Riociguat treatment continues or at most for more 6 years. The purpose is to collect information on safety and effectiveness, such as adverse events and clinical worsening of PAH, once a year. Combining the standard observation and the extension observation period the patient could be followed for at most 7 years. When Riociguat treatment is terminated, the observation of the patient ends. The investigator should record data for each patient, as defined in the protocol, using the Electronic Data Capture (EDC) system. The duration of the study is of approximately 8 years from PAH indication approval.

Official Title
-----------------
Drug Use Investigation of Riociguat for Pulmonary Arterial Hypertension (PAH)

Conditions
-----------------
Hypertension, Pulmonary

Intervention / Treatment
-----------------
* Drug: Riociguat (ADEMPAS, BAY63-2521)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who are treated with Riociguat for PAH Exclusion Criteria: N/A
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Riociguat<br>Riociguat treatment group | Drug: Riociguat (ADEMPAS, BAY63-2521)<br>* The treatment of Riociguat should comply with the local product information<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events. Adverse events of special interest:Hypotension,Gastrointestinal disorder,Hemoptysis, pulmonary hemorrhage and Pulmonary congestion, pulmonary edema |  | Up to 7 years | 
| Number of participants with adverse drug reaction |  | Up to 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 6-Minute Walking Distance at 3 months and 12 months |  | Baseline and 3 months,Baseline and 12 months | 
| Change from baseline in Pulmonary Vascular Resistance (PVR) after 3 and 12 months |  | Baseline and 3 months,Baseline and 12 months | 
| Change from baseline in tricuspid regurgitation pressure gradient (TRPG) after 3 and 12 months |  | Baseline and 3 months,Baseline and 12 months | 
| Change in blood concentration from baseline in brain natriuretic peptide / N-terminal pro-brain natriuretic peptide (BPN/NT-pro BNP) after 3 and 12 months. |  | Baseline and 3 months,Baseline and 12 months | 
| Change from baseline in WHO functional class after 3 and 12 months |  | Baseline and 3 months,Baseline and 12 months | 
| Time to Clinical Worsening | The 1st occurrence of the following events is recorded & will considered for the calculation of the combined endpoint : -Death (all-cause mortality)-Heart/lung transplantation -Atrial Septostomy -Hospitalization due to persistent worsening of Pulmonary Hypertension -Start of new PH specific treatment (endothelin receptor antagonists, prostacycline analogues)or modification of a preexisting Prostacycline analogues treatment)due to worsening Pulmonary Hypertension (WPH) -Persistent decrease in 6MWD due to WPH (e.g. more than 15 % from baseline or more than 30% compared to the last measurement) | Up to 7 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Riociguat, Adempas, soluble guanylate cyclase (sGC) stimulator, Pulmonary arterial hypertension, Japan, Post-marketing surveillance