MedPath

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

Phase 4
Terminated
Conditions
Pulmonary Arterial Hypertension
Interventions
Other: PAH Therapies
Registration Number
NCT04955990
Lead Sponsor
Actelion
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
232
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with PAHPAH TherapiesParticipants with pulmonary arterial hypertension (PAH) who newly initiate any PAH therapy(ies) at the index date (date when a participant starts the first new PAH therapy after baseline assessments) in a routine clinical setting, either as first-line therapy, as replacement therapies, as concomitant with other PAH therapies, or have already been receiving macitentan 10 milligrams (mg) for at least 3 months prior to the index date. The primary data source for this study will be the medical records of each participant.
Primary Outcome Measures
NameTimeMethod
Time to all Cause DeathUp to 6 years

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

Time to Death due to Pulmonary Arterial Hypertension (PAH) or First Hospitalization due to PAHUp to 6 years

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

Secondary Outcome Measures
NameTimeMethod
Time to First all-cause HospitalizationUp to 6 years

Time to first all-cause hospitalization will be reported.

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

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 to Worsening in WHO FCUp to 6 months

Time to worsening in WHO FC will be reported.

Time to Death due to PAHUp to 6 years

Time to death due to PAH will be reported.

Time to First Morbidity/Mortality EventUp to 6 years

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 to Clinical WorseningUp to 6 years

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.

Medical Resource UtilizationUp to 6 years

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.

Change from Baseline in World Health Organization (WHO) Functional Class (FC)Baseline up to 6 years

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).

Risk Assessment Strategies for Clinical Worsening or DeathUp to 6 years

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.

Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by Symptoms and Impact Questionnaire for Use in Clinical Practice (SYMPACT-CP) QuestionnaireBaseline up to 6 years

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.

Change from Baseline in N-terminal-pro-hormone Brain Natriuretic Peptide (NT-proBNP)Baseline up to 6 years

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).

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

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

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 VariablesBaseline up to 6 years

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.

Change from Baseline in Number of Participants Within Each Overall Risk Category (Low, Intermediate, or High) According to the Noninvasive CriteriaBaseline up to 6 years

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 to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 1Up to 6 years

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

Change from Baseline in Medication Adherence Questions of each Prescribed PAH Therapy ClassBaseline up to 6 years

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

Time to all-cause Death Based on the Number of low-risk Noninvasive criteria Based on WHO FC, 6MWD, and NT-proBNPUp 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 will be reported.

Time to all-cause Death Based on the Risk Category Determined by the Noninvasive CriteriaUp to 6 years

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

Change from Baseline in Health-Related Quality of life Status as Assessed by 36-item Short-Form Health Survey (SF-36) v2 Acute QuestionnaireBaseline up to 6 years

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).

Change from Baseline in PAH-specific Medication Adherence as Assessed by Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) QuestionnaireBaseline up to 6 years

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.

Change from Baseline in Patient Global Assessment of Disease Severity (PGA-S) of PAHBaseline up to 6 years

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 to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 2Up to 6 years

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

Change from Baseline in PAH-specific Medication Adherence as Assessed by Morisky Medication Adherence Scale-8 (MMAS-8) ScoreBaseline up to 6 years

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.

PAH Symptoms and Impact using SYMPACT-CP QuestionnaireBaseline up to 6 years

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

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

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)Baseline up to 6 years

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.

Trial Locations

Locations (54)

University Of Iowa - Hospitals & Clinics

🇺🇸

Iowa City, Iowa, United States

London Health Sciences Centre Victoria Hospital

🇨🇦

London, Ontario, Canada

Severance Hospital Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

The Catholic University of Korea Seoul St Mary s Hospital

🇰🇷

Seoul, Korea, Republic of

Wojewodzki Szpital Specjalistyczny im Stefana Kardynala Wyszynskiego SPZOZ

🇵🇱

Lublin, Poland

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 Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

Kentuckiana Pulmonary Associates

🇺🇸

Louisville, Kentucky, United States

University of Maryland

🇺🇸

Baltimore, Maryland, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Mayo Clinic - Rochester

🇺🇸

Rochester, Minnesota, United States

University of Missouri

🇺🇸

Columbia, Missouri, United States

University of New Mexico

🇺🇸

Albuquerque, New Mexico, United States

University of Cinncinnati Physicans- UC Health Physicnas Office

🇺🇸

Cincinnati, Ohio, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Houston Methodist Hospital

🇺🇸

Houston, Texas, United States

Instituto Cardiovascular de Rosario

🇦🇷

Rosario, Argentina

Universidade Federal De Minas Gerais - Hospital das Clínicas

🇧🇷

Belo Horizonte, Brazil

Universidade Estadual Paulista 'Julio De Mesquita Filho'

🇧🇷

Botucatu, Brazil

Irmandade Santa Casa de Misericordia de Porto Alegre

🇧🇷

Porto Alegre, Brazil

Hospital Das Clinicas Da Faculdade De Medicina Da USP

🇧🇷

Sao Paulo, Brazil

University of Alberta Hospital

🇨🇦

Edmonton, Alberta, Canada

Beijing Anzhen Hospital

🇨🇳

Beijing, China

Beijing Fuwai Hospital

🇨🇳

Beijing, China

Peking Union Medical College Hospital

🇨🇳

Beijing, China

West China Hospital Sichuan University

🇨🇳

Chengdu, China

Shanghai Pulmonary Hospital

🇨🇳

Shanghai, China

Universitatsklinikum Bonn

🇩🇪

Bonn, Germany

Ospedale S.Giuseppe, Gruppo MultiMedica

🇮🇹

Milano, Italy

IRCCS Policlinico San Matteo, Università degli studi di Pavi

🇮🇹

Pavia, Italy

Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma

🇮🇹

Rome, Italy

National Hospital Organization Okayama Medical Center

🇯🇵

Okayama, Japan

Pusan National University Hospital

🇰🇷

Busan, Korea, Republic of

Gachon University Gil Medical Center

🇰🇷

Incheon, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

National Heart Institute

🇲🇾

Kuala Lumpur, Malaysia

Vrije Universiteit Amsterdam (VU)

🇳🇱

Amsterdam, Netherlands

Sint Antonius Ziekenhuis

🇳🇱

Nieuwegein, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Krakowski Szpital Specjalistyczny im Jana Pawla II

🇵🇱

Krakow, Poland

CardioPulmonary Research, PSC

🇵🇷

Guaynabo, Puerto Rico

National Heart Centre (NHC) Singapore

🇸🇬

Singapore, Singapore

Hosp. Univ. 12 de Octubre

🇪🇸

Madrid, Spain

Hosp. Univ. Pta. de Hierro Majadahonda

🇪🇸

Majadahonda, Spain

Hosp. Univ. Marques de Valdecilla

🇪🇸

Santander, Spain

Sahlgrenska Universitetsjukhuset

🇸🇪

Goeteborg, Sweden

Royal Free Hospital

🇬🇧

London, United Kingdom

Hammersmith Hospital

🇬🇧

London, United Kingdom

Freeman Hospital

🇬🇧

Newcastle upon Tyne, United Kingdom

Papworth Hospital, Cambridge University

🇬🇧

Papworth Everard, United Kingdom

Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital

🇬🇧

Sheffield, United Kingdom

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