A Study to Learn About How Well Riociguat Works, How Safe it is and How it is Used Under Real World Conditions in Patients in the United States Who Are Receiving Riociguat for High Blood Pressure in the Arteries That Carry Blood From the Heart to the Lungs (Pulmonary Arterial Hypertension, PAH) (ROAR)

RiOciguAt UseRs Registry

Pulmonary arterial hypertension (PAH) is a type of high blood pressure in the arteries that carry blood from the heart to the lungs. PAH occurs when the openings in the blood vessels of the lungs get smaller and smaller. These smaller openings can be caused by the following:

• The walls of the arteries tightening
• The walls of the arteries becoming stiff and narrow from an overgrowth of cells The increased pressure in the pulmonary arteries strains the right side of the heart and it begins to fail, causing difficulty breathing and other symptoms. As PAH progresses, symptoms get worse.

There is no cure for PAH, but several medications like endothelin receptor antagonists (ERAs), prostacyclin analogues (PCAs) and riociguat, a soluable guanylate cyclase stimulator, are available to help slow the progression of changes in the pulmonary arteries and help reduce symptoms. Riociguat can be taken together with ERAs and PCAs.

In this study, the researchers want to learn about how well riociguat works, how safe it is when patients take it in 1 of these ways:

• alone
• with ERA
• with PCA
• with ERA and PCA The dosage for each patient will be decided by their doctor. The researchers will review information collected from the patients who have decided with their doctor to start riociguat treatment for their PAH. The study will include about 500 patients in the United States who are at least 18 years old. All of the patients will have either just started taking riociguat or will have been taking it for less than 3 months No investigational products will be administered in this study. Patients will be treated with the Standard of Care (SOC) for PAH. The SOC is the currently appropriate treatment in accordance with scientific evidence and agreed upon in collaboration between medical experts for PAH. There will be no study-mandated visits or treatments.

The patients will be in the study for up to 2 years. During this time, they will visit their doctor every 3 to 6 months as part of the Standard of Care. At these visits, the patients will answer questions about their PAH symptoms and whether they have any medical problems. They will also do exercise tests to see how well they are able to breathe and how tired they get while exercising. The doctors will perform other usual examinations which are part of the Standard of Care such as echocardiograms (images of the heart to show how the heart is working) and a right heart catheters (to measure the pressures in the heart) and will take the usual blood and urine samples.

Study Overview

• Status: Active, not recruiting
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: Riociguat (Adempas, BAY63-2521)

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Alliance Pulmonary
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center- Phoenix
    • Phoenix, Arizona, United States, 85020
      • Honor Health
    • Tucson, Arizona, United States, 85719
      • Univ of Arizona College of Medicine, Tucson
  • California
    • Fresno, California, United States, 93710
      • UCSF
    • Irvine, California, United States, 92697
      • UC Irvine
    • Los Angeles, California, United States, 90089
      • USC
    • Los Angeles, California, United States, 90048
      • Cedar Sinai
    • Sacramento, California, United States, 95817
      • UC Davis
    • San Diego, California, United States, 92103
      • UCSD
    • Santa Barbara, California, United States, 93105
      • Santa Barbara Cottage Hospital
  • Florida
    • Orlando, Florida, United States, 32808
      • Advent Health
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital USF
    • Weston, Florida, United States, 33331
      • CCF (Cleveland Clinic Florida)
  • Georgia
    • Columbus, Georgia, United States, 31904
      • St Francis Medical Ctr
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern
    • Maywood, Illinois, United States, 60153
      • Loyola
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • KUMC
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Pulmonary Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston University
    • Boston, Massachusetts, United States, 02210
      • Mass General
  • Michigan
    • Troy, Michigan, United States, 48085
      • Beaumont Hospital
  • Missouri
    • Columbia, Missouri, United States, 30309
      • University of Missouri
    • Saint Louis, Missouri, United States, 63103
      • St. Louis University
    • Saint Louis, Missouri, United States, 63108
      • Barnes / Wash U
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • UNMC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87114
      • UNMH
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop
    • New Hyde Park, New York, United States, 11042
      • Northwell Health
    • New York, New York, United States, 10016
      • NYU Langone
    • New York, New York, United States, 10032
      • Columbia
    • New York, New York, United States, 10003
      • Mount Sinai
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • University of Cincinnati
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris
  • Oregon
    • Portland, Oregon, United States, 97232
      • Legacy Health
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Medical Center
  • Texas
    • Austin, Texas, United States, 78759
      • Seton Heart
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Denison, Texas, United States, 75020
      • Premier Pulmonary
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Plano, Texas, United States, 75093
      • Baylor Scott and White
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Richmond Pulmonary Associates
    • Richmond, Virginia, United States, 23219
      • VCU/MCV
  • Washington
    • Spokane, Washington, United States, 99208
      • Providence
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert/Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Advocate Aurora

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

US patients aged ≥18 years, diagnosed with PAH, who are naïve to and initiating treatment with riociguat as per the FDA approved US label for PAH - either at study enrollment or have initiated riociguat within 90 days prior to study enrollment.

Description

Inclusion Criteria:

• Patients aged ≥18 years at the time of riociguat treatment initiation
• Diagnosis of PAH per National Institute for Health and Care Excellence (NICE) 2018 classification
• Decision to initiate treatment with riociguat as per investigator's routine treatment practice made prior to enrollment in the study

• Initiation of riociguat, as per the FDA-approved US label:

  • At enrollment OR
  • ≤90 days prior to enrollment, with a documented titration regimen (defined as all documented dose changes including, but not limited to: starting dose and dates and highest tolerated dose and dates)
• Signed informed consent

Exclusion Criteria:

• Previously treated with and discontinued use of riociguat for any reason prior to study enrollment (discontinuation defined as an interruption of therapy ≥30 days)

• Participating in any of the following:

  1. Blinded clinical trial
  2. Clinical trial involving an unapproved drug
  3. Investigational program with interventions outside of routine clinical practice
• Life expectancy <12 months
• Contraindicated to receive riociguat per the FDA approved US label
• Use of nitrates or NO donors in any form
• Use of PDE5 inhibitors
• PH associated with idiopathic interstitial pneumonias
• Unable or unwilling to provide informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients diagnosed with PAH	Drug: Riociguat (Adempas, BAY63-2521); Follow clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs)		Up to 24 months
Change of 6-minute walk distance (6MWD) from baseline to Months 6, 12, and 24		At baseline, Month 6, 12, and 24
Change of NT-proBNP from baseline to Months 6, 12, and 24	NT-proBNP: N-terminal pro-hormone B-type natriuretic peptide	At baseline, Month 6, 12, and 24
Change of BNP from baseline to Months 6, 12, and 24	BNP: B-type natriuretic peptide	At baseline, Month 6, 12, and 24
Change of clinical PAH scores from baseline to Months 6, 12, and 24		At baseline, Month 6, 12, and 24
Change of hemodynamic measurements from RHC from baseline to Months 6, 12, and 24	RHC: Right-heart catheterization	At baseline, Month 6, 12, and 24
Change of ECHO measurements from baseline to Months 6, 12, and 24	ECHO: Echocardiogram	At baseline, Month 6, 12, and 24
Change of laboratory tests from baseline to Months 6, 12, and 24		At baseline, Month 6, 12, and 24
Change of NYHA/WHO PH functional class from baseline to Months 6, 12, and 24	NYHA: New York Heart Association WHO: World Health Organization	At baseline, Month 6, 12, and 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to Month 6 and change from baseline to Month 12 in Borg Dysponea Index	At baseline, Month 6 and Month 12
Change from baseline to Month 6 and change from baseline to Month 12 in emPHasis-10	At baseline, Month 6 and Month 12
Persistence/discontinuation rates for riociguat	Up to 24 months
Reasons for discontinuation of riociguat	At Month 6, 12, and 24 post-baseline
Real-world treatment patterns for riociguat for PAH	Up to 24 months
Demographic of patients treated with riociguat	Up to 24 months
Clinical characteristics of patients treated with riociguat	Up to 24 months

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Xcenda, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2021
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Activators; Riociguat
• Other Study ID Numbers: 21427

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No