A Study of Real-world Cohort of Pulmonary Arterial Hypertension (PAH) Participants

Phase 4TerminatedNCT04955990

Actelion232 enrolled

Overview

This study is designed to describe pulmonary arterial hypertension (PAH) participants in terms of their clinical characteristics, therapies used, disease progression, and outcomes (example, death, hospitalization, risk category for predicted mortality risk, 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 studies to address relevant research questions (example, 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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

232

Conditions

Pulmonary Arterial Hypertension

Interventions

No Drug will be administered as part of this study. Real world data will be collected in participants who newly initiate PAH therapies in routine clinical setting or have already been receiving macitentan 10 mg for at least 3 months prior to the index date.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Symptomatic pulmonary arterial hypertension (PAH) in any PAH subtype * PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to or at the index date fulfilling all of the criteria below: a) Mean pulmonary artery pressure greater than (\>) 20 millimeters of mercury (mm Hg), and b) Pulmonary artery wedge pressure or left ventricular end diastolic pressure less than or equal to (\<=) 15 mm Hg, and c) Pulmonary vascular resistance greater than or equal to (\>=) 3 Wood Units (that is, \>= 240 dynes seconds per centimeters penta \[dyn∙sec/cm\^5\]) * Participant satisfies either a or b: a) Newly initiating 1 or more PAH therapy(ies) (as monotherapy or add-on therapy) at index date. These newly initiated PAH therapies should not have been used within 3 months of the index date; b) Taking macitentan 10 milligrams (mg) therapy (as monotherapy or in combination) with no changes in PAH therapy for within 3 months prior to the index date * All mandated assessments must be performed and recorded at the baseline visit before the initiation of the new PAH therapy at the index date or enrollment in the study. * For the pulmonary arterial hypertension-symptoms and impact (PAH-SYMPACT) substudy only: Participants initiating any endothelin receptor antagonist (ERA) or phosphodiesterase-5 inhibitor therapies at index date or at therapy change must provide consent to enroll in the optional PAH-SYMPACT substudy. Refusal to give consent for the optional PAH-SYMPACT substudy will not exclude a participant from participation in the main study Exclusion Criteria: * Participants enrolled in any interventional clinical trial with an investigational therapy in the 3-month period prior to index date * Currently enrolled in an observational study sponsored or managed by a Janssen company * Presence of moderate or severe obstructive lung disease (forced expiratory volume in 1 second \[FEV1\] / forced vital capacity \[FVC\] \<70%; and FEV1 \<60% of predicted after bronchodilator administration) in participants with a known or suspected history of significant lung disease, as documented by a spirometry test performed within 1 year prior to screening * Presence of moderate or severe restrictive lung disease (for example, total lung capacity or FVC \<60 percent \[%\] of normal predicted value) in participants with a known or suspected history of significant lung disease, as documented by a spirometry test performed within 1 year prior to screening

Locations (54)

Bay Area Cardiology Associates, P.A. - Brandon Office

Brandon, Florida, United States

University of South Florida

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

University Of Iowa - Hospitals & Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Outcomes

Primary Outcomes

Time to all Cause Death

Time to all cause death will be reported. All-cause death defined as deaths due to any cause.

Time frame: Up to 6 years

Time to Death due to Pulmonary Arterial Hypertension (PAH) or First Hospitalization due to PAH

Time to death due to PAH or first hospitalization due to PAH will be reported.

Time frame: Up to 6 years

Secondary Outcomes

Time to Death due to PAH

Time to death due to PAH will be reported.

Time frame: Up to 6 years

Time to First all-cause Hospitalization

Time to first all-cause hospitalization will be reported.

Time frame: Up to 6 years

Time to First Morbidity/Mortality Event

Time to first morbidity/mortality event will be reported. All-cause death, non-planned hospitalization due to PAH (including for worsening of PAH, atrial septostomy, lung transplantation with or without heart transplantation, or initiation of parenteral prostacyclins), PAH-related disease progression, defined as (both criteria must be satisfied): At least 15 percent (%) decrease in 6-minute walking distance (6MWD) from baseline or therapy change visit, and initiation of additional PAH therapy or worsening of World Health Organization (WHO) functional class (FC) will be collected for morbidity/mortality events assessment.

Time frame: Up to 6 years

Time to Clinical Worsening

Time to clinical worsening will be reported. All-cause death, non-planned hospitalization due to PAH (including for worsening of PAH, atrial septostomy, lung transplantation with or without heart transplantation, or initiation of parenteral prostacyclins), PAH-related deterioration identified by at least 1 criterion: worsening of WHO FC, deterioration by at least 15% in exercise capacity, as measured by the 6MWD, any signs or symptoms of right-sided heart failure will be collected for clinical worsening assessment.

Time frame: Up to 6 years

Medical Resource Utilization

Number per year of all-cause and PAH-related hospitalizations; number per year of in-patient hospital days for all causes and PAH-related causes; number per year of emergency room visits for all causes and for PAH-related causes that do not result in hospital admittance will be collected for assessment of medical resource utilization.

Time frame: Up to 6 years

Change from Baseline in 6-minute Walk Distance (6MWD)

Change from baseline in 6MWD according to non-invasive criteria will be assessed as per the low (greater than \[\>\] 440 meters \[m\]), intermediate (165-440m), and high-risk category (less than \[\<\] 165m).

Time frame: Baseline up to 6 years

Change from Baseline in World Health Organization (WHO) Functional Class (FC)

Change from baseline in WHO FC according to non-invasive criteria will be assessed as per the low (I, II), intermediate (III), and high-risk category (IV).

Time frame: Baseline up to 6 years

Change from Baseline in N-terminal-pro-hormone Brain Natriuretic Peptide (NT-proBNP)

Change from baseline in NT-proBNP according to non-invasive criteria will be assessed as per the low (\<300 nanogram per liters \[ng/l\]), intermediate (300-1400ng/l), and high-risk category (\>1400 ng/l).

Time frame: Baseline up to 6 years

Time to Worsening in WHO FC

Time to worsening in WHO FC will be reported.

Time frame: Up to 6 months

Change from Baseline in the Number of low-risk Noninvasive Criteria Based on WHO FC, 6MWD, and NT-proBNP

Change from baseline in the number of low-risk noninvasive criteria based on WHO FC, 6MWD, and NT-proBNP will be reported.

Time frame: Baseline up to 6 years

Time to all-cause Death Based on the Number of low-risk Noninvasive criteria Based on WHO FC, 6MWD, and NT-proBNP

Time to all-cause death based on the number of low-risk noninvasive criteria based on WHO FC, 6MWD, and NT-proBNP will be reported.

Time frame: Up to 6 years

Change from Baseline in Number of Participants Within Each Overall Risk Category (Low, Intermediate, or High) According to the Noninvasive Criteria

Change from baseline in number of participants within each overall risk category (low, intermediate, or high) according to low-risk non-invasive criteria will be assessed as per the following parameters: WHO FC- low (I, II), intermediate (III), and high-risk category (IV); 6MWD- low (\> 440m), intermediate (165-440m), and high-risk category (\< 165m), and \<165m; and NT-proBNP- low (\<300ng/l), intermediate (300-1400ng/l), and high-risk category (\>1400 ng/l).

Time frame: Baseline up to 6 years

Change from Baseline in Number of Participants Within Each Overall Risk Category (low, Intermediate, or High) According to Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) Lite 1 Variables

Change from baseline in number of participants within each overall risk category (low, Intermediate, or High) according to REVEAL Lite 1 Variables will be reported. The REVEAL Lite 1 variables risk calculator determines the risk status, and the scores (ranges from 0 to 19) can be defined as: low risk as a score of less than or equal to (\<=) 6, intermediate risk as a score of 7 or 8, and high risk as a score of greater than or equal to (\>=) 9 for the survival rates.

Time frame: Baseline up to 6 years

Change from Baseline in Number of Participants Within Each Overall Risk Category (low, Intermediate, or High) According to REVEAL Lite 2 Variables

Change from baseline in number of participants within each overall risk category (low, Intermediate, or High) according to REVEAL Lite 2 Variables will be reported. The REVEAL Lite 2 variables risk calculator determines the risk status, and the scores (ranges from 1 to 14) can be defined as: low risk as a score of \<= 5, intermediate risk as a score of 6 or 7, and high risk as a score of \>= 8 for the survival rates.

Time frame: Baseline up to 6 years

Time to all-cause Death Based on the Risk Category Determined by the Noninvasive Criteria

Time to all-cause death based on the risk category determined by the noninvasive criteria will be reported.

Time frame: Up to 6 years

Time to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 1

Time to all-cause death based on the risk category determined by the REVEAL Lite 1 will be reported.

Time frame: Up to 6 years

Time to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 2

Time to all-cause death based on the risk category determined by the REVEAL Lite 2 will be reported.

Time frame: Up to 6 years

Risk Assessment Strategies for Clinical Worsening or Death

The assessment of risk category for clinical worsening and death will be assessed by the following 3 risk assessment strategies: number of low-risk noninvasive criteria based on WHO FC, 6MWD, and NT-proBNP.

Time frame: Up to 6 years

Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by Symptoms and Impact Questionnaire for Use in Clinical Practice (SYMPACT-CP) Questionnaire

A modified version of the PAH-SYMPACT for Use in Clinical Practice (SYMPACT-CP), has been created for use in routine clinical practice, as an assessment to support symptom monitoring and guide treatment decisions by healthcare providers. In the SYMPACT-CP, the 24-hour recall period for the oxygen use item and the 11 symptoms items have been modified to a 1-week recall period. The SYMPACT-CP also includes 11 impact items (with a 1-week recall period). This modification was made with the intention of administering the questionnaire at a single timepoint.

Time frame: Baseline up to 6 years

Change from Baseline in Health Related Quality of Life Assessed by European Quality of Life (EuroQoL) Group, 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)

The EQ-5D-5L is an instrument to measure health-related quality of life consisting of a descriptive system and visual analogue scale (VAS). The descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels of perceived problems (1 indicating no problem, 2 indicating slight problems, 3 indicating moderate problems, 4 indicating severe problems, 5 indicating extreme problems). Participant selects an answer for each of 5 dimensions considering the response that best matches his or her health "today". The responses to the 5 dimensions are used to compute a single score ranging from 0 (worst health state) to 100 (better health state) representing the general health status of the individual.

Time frame: Baseline up to 6 years

Change from Baseline in Health-Related Quality of life Status as Assessed by 36-item Short-Form Health Survey (SF-36) v2 Acute Questionnaire

The SF-36 v2 acute questionnaire is a 36-item short form survey used to assess the participant's quality of life. In the SF-36 v2 Acute Questionnaire, participants are instructed to rate their health and capacity to perform activities of daily living in eight domains including physical functioning, physical role limitations, bodily pain, general health, vitality, social functioning, emotional role limitations, and mental health during the last week. The scores range from 0 (lowest or worst possible level of functioning) to 100 (highest or best possible level of functioning).

Time frame: Baseline up to 6 years

Change from Baseline in PAH-specific Medication Adherence as Assessed by Morisky Medication Adherence Scale-8 (MMAS-8) Score

The MMAS-8 is commonly used in standard clinical practice and a validated measure of treatment adherence. The MMAS-8 includes 8 questions assessing the extent of adherence or nonadherence and reasons for non-adherence.

Time frame: Baseline up to 6 years

Change from Baseline in Medication Adherence Questions of each Prescribed PAH Therapy Class

Change from baseline in medication adherence questions of each prescribed PAH therapy class will be reported.

Time frame: Baseline up to 6 years

Change from Baseline in PAH-specific Medication Adherence as Assessed by Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire

The PAH-SYMPACT questionnaire, applicable only for participants who enrolled in the PAH-SYMPACT substudy, is a PRO instrument and composed of 2 parts: the symptoms part and the Impacts part. There is no total symptom score; the 2 domains are: cardiopulmonary symptoms and cardiovascular symptoms. The Impacts part has 2 domains: Physical Impacts Domain and Cognitive/Emotional Impacts Domain which contain 7 and 4 items, respectively. Each item has 5-point Likert response scale (0=not at all, 1=mild, 2=moderate, 3=severe, and 4=very severe). The mean individual weekly symptom item scores are aggregated by domain, with the sum then being divided by the number of symptom items in the respective domain. This leads to the average weekly domain score ranging from 0-4 for each participant with higher scores indicating greater symptom severity or worse impact.

Time frame: Baseline up to 6 years

Change from Baseline in Patient Global Assessment of Disease Severity (PGA-S) of PAH

Change from baseline in PGA-S of PAH will be reported. It includes severity of PAH symptoms, such as, none, mild, moderate, severe and very severe.

Time frame: Baseline up to 6 years

PAH Symptoms and Impact using SYMPACT-CP Questionnaire

PAH symptoms and impact using SYMPACT-CP questionnaire will be reported.

Time frame: Baseline up to 6 years