Clinical trial NCT04813926: 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)
Official title: RiOciguAt UseRs Registry
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pulmonary Arterial Hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Xcenda, LLC
First posted: 2021-03-24
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 24 months
measure: Change of 6-minute walk distance (6MWD) from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of NT-proBNP from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of BNP from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of clinical PAH scores from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of hemodynamic measurements from RHC from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of ECHO measurements from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of laboratory tests from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
measure: Change of NYHA/WHO PH functional class from baseline to Months 6, 12, and 24
timeFrame: At baseline, Month 6, 12, and 24
Secondary outcomes:
measure: Change from baseline to Month 6 and change from baseline to Month 12 in Borg Dysponea Index
timeFrame: At baseline, Month 6 and Month 12
measure: Change from baseline to Month 6 and change from baseline to Month 12 in emPHasis-10
timeFrame: At baseline, Month 6 and Month 12
measure: Persistence/discontinuation rates for riociguat
timeFrame: Up to 24 months
measure: Reasons for discontinuation of riociguat
timeFrame: At Month 6, 12, and 24 post-baseline
measure: Real-world treatment patterns for riociguat for PAH
timeFrame: Up to 24 months
measure: Demographic of patients treated with riociguat
timeFrame: Up to 24 months
measure: Clinical characteristics of patients treated with riociguat
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner University Medical Center- Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Honor Health
state: Arizona
city: Tucson
country: United States
facility: Univ of Arizona College of Medicine, Tucson
state: Arizona
city: Fresno
country: United States
facility: UCSF
state: California
city: Irvine
country: United States
facility: UC Irvine
state: California
city: Los Angeles
country: United States
facility: Cedar Sinai
state: California
city: Los Angeles
country: United States
facility: USC
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: San Diego
country: United States
facility: UCSD
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Orlando
country: United States
facility: Advent Health
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital USF
state: Florida
city: Weston
country: United States
facility: CCF (Cleveland Clinic Florida)
state: Florida
city: Columbus
country: United States
facility: St Francis Medical Ctr
state: Georgia
city: Chicago
country: United States
facility: Northwestern
state: Illinois
city: Maywood
country: United States
facility: Loyola
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ
state: Illinois
city: Kansas City
country: United States
facility: KUMC
state: Kansas
city: Louisville
country: United States
facility: Norton Pulmonary Specialists
state: Kentucky
city: Boston
country: United States
facility: Mass General
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Troy
country: United States
facility: Beaumont Hospital
state: Michigan
city: Columbia
country: United States
facility: University of Missouri
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Barnes / Wash U
state: Missouri
city: Omaha
country: United States
facility: UNMC
state: Nebraska
city: Albuquerque
country: United States
facility: UNMH
state: New Mexico
city: Mineola
country: United States
facility: Winthrop
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: NYU Langone
state: New York
city: New York
country: United States
facility: Columbia
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Oklahoma City
country: United States
facility: Integris
state: Oklahoma
city: Portland
country: United States
facility: Legacy Health
state: Oregon
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Medical Center
state: South Carolina
city: Austin
country: United States
facility: Seton Heart
state: Texas
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Denison
country: United States
facility: Premier Pulmonary
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Plano
country: United States
facility: Baylor Scott and White
state: Texas
city: Richmond
country: United States
facility: Richmond Pulmonary Associates
state: Virginia
city: Richmond
country: United States
facility: VCU/MCV
state: Virginia
city: Spokane
country: United States
facility: Providence
state: Washington
city: Milwaukee
country: United States
facility: Advocate Aurora
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert/Medical College of Wisconsin
state: Wisconsin
city: Guaynabo
country: Puerto Rico
facility: Alliance Pulmonary
Study officials:
References: