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



Sponsor:   Actelion


Sommario: 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.




TIPOLOGIA STUDIO

 
Interventistico



FASE

 
Fase 4




TRATTAMENTO

  
    
  






OBIETTIVO PRIMARIO


  
  • Misura: Time to all Cause Death
  • Tempo: Up to 6 years
  • Descrizione: Time to all cause death will be reported. All-cause death defined as deaths due to any
cause.
  • Misura: Time to Death due to Pulmonary Arterial Hypertension (PAH) or First Hospitalization due to PAH
  • Tempo: Up to 6 years
  • Descrizione: Time to death due to PAH or first hospitalization due to PAH will be reported.




OBIETTIVO SECONDARIO


  
  • Misura: Time to Death due to PAH
  • Tempo: Up to 6 years
  • Descrizione: Time to death due to PAH will be reported.
  • Misura: Time to First all-cause Hospitalization
  • Tempo: Up to 6 years
  • Descrizione: Time to first all-cause hospitalization will be reported.
  • Misura: Time to First Morbidity/Mortality Event
  • Tempo: Up to 6 years
  • Descrizione: 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.
  • Misura: Time to Clinical Worsening
  • Tempo: Up to 6 years
  • Descrizione: 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.
  • Misura: Medical Resource Utilization
  • Tempo: Up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in 6-minute Walk Distance (6MWD)
  • Tempo: Baseline up to 6 years
  • Descrizione: 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).
  • Misura: Change from Baseline in World Health Organization (WHO) Functional Class (FC)
  • Tempo: Baseline up to 6 years
  • Descrizione: 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).
  • Misura: Change from Baseline in N-terminal-pro-hormone Brain Natriuretic Peptide (NT-proBNP)
  • Tempo: Baseline up to 6 years
  • Descrizione: 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).
  • Misura: Time to Worsening in WHO FC
  • Tempo: Up to 6 months
  • Descrizione: Time to worsening in WHO FC will be reported.
  • Misura: Change from Baseline in the Number of low-risk Noninvasive Criteria Based on WHO FC, 6MWD, and NT-proBNP
  • Tempo: Baseline up to 6 years
  • Descrizione: Change from baseline in the number of low-risk noninvasive criteria based on WHO FC,
6MWD, and NT-proBNP will be reported.
  • Misura: Time to all-cause Death Based on the Number of low-risk Noninvasive criteria Based on WHO FC, 6MWD, and NT-proBNP
  • Tempo: Up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in Number of Participants Within Each Overall Risk Category (Low, Intermediate, or High) According to the Noninvasive Criteria
  • Tempo: Baseline up to 6 years
  • Descrizione: 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).
  • Misura: 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
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in Number of Participants Within Each Overall Risk Category (low, Intermediate, or High) According to REVEAL Lite 2 Variables
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: Time to all-cause Death Based on the Risk Category Determined by the Noninvasive Criteria
  • Tempo: Up to 6 years
  • Descrizione: Time to all-cause death based on the risk category determined by the noninvasive criteria
will be reported.
  • Misura: Time to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 1
  • Tempo: Up to 6 years
  • Descrizione: Time to all-cause death based on the risk category determined by the REVEAL Lite 1 will
be reported.
  • Misura: Time to all-cause Death Based on the Risk Category Determined by the REVEAL Lite 2
  • Tempo: Up to 6 years
  • Descrizione: Time to all-cause death based on the risk category determined by the REVEAL Lite 2 will
be reported.
  • Misura: Risk Assessment Strategies for Clinical Worsening or Death
  • Tempo: Up to 6 years
  • Descrizione: 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.
  • Misura: 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
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: 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)
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in Health-Related Quality of life Status as Assessed by 36-item Short-Form Health Survey (SF-36) v2 Acute Questionnaire
  • Tempo: Baseline up to 6 years
  • Descrizione: 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).
  • Misura: Change from Baseline in PAH-specific Medication Adherence as Assessed by Morisky Medication Adherence Scale-8 (MMAS-8) Score
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in Medication Adherence Questions of each Prescribed PAH Therapy Class
  • Tempo: Baseline up to 6 years
  • Descrizione: Change from baseline in medication adherence questions of each prescribed PAH therapy
class will be reported.
  • Misura: Change from Baseline in PAH-specific Medication Adherence as Assessed by Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: Change from Baseline in Patient Global Assessment of Disease Severity (PGA-S) of PAH
  • Tempo: Baseline up to 6 years
  • Descrizione: 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.
  • Misura: PAH Symptoms and Impact using SYMPACT-CP Questionnaire
  • Tempo: Baseline up to 6 years
  • Descrizione: PAH symptoms and impact using SYMPACT-CP questionnaire will be reported.




CRITERI DI ELIGIBILITA'


    
             
  • 
        Criteri di inclusione e esclusione
        
    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
    
        
    • 
    




SESSO

  
Tutti




  


ETA' MINIMA



Età Minima: 18 Years

Età Massima: N/A






LUOGO


  
Ospedale S.Giuseppe, Gruppo MultiMedica
Milan	6951411, 20123
IRCCS Policlinico San Matteo, Università degli studi di Pavi
Pavia	3171366, 27100
Universita degli Studi di Roma 'La Sapienza' - Umberto I Policlinico di Roma
Rome	3169070, 00161