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

Pulmonary Arterial Hypertension Clinical Trial

— CARE PAH  

Official title:

An International, Non-Drug Interventional, Real-world Cohort of PAH Patients Newly Initiating PAH Therapy With Guideline-directed Assessments of Disease Severity

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04955990
• Other study ID #: CR109007
• Secondary ID: 67896062PAH4005
• Status: Terminated
• Phase: Phase 4
• Start date: October 14, 2021
• Est. completion date: December 20, 2022

Study information

• Verified date: March 2024
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 232
• Est. completion date: December 20, 2022
• Est. primary completion date: December 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Other:
• PAH Therapies
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.

Locations

Country	Name	City	State
Argentina	Instituto Cardiovascular de Rosario	Rosario
Brazil	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
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
China	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
Germany	Universitatsklinikum Bonn	Bonn
Italy	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
Japan	National Hospital Organization Okayama Medical Center	Okayama
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul
Malaysia	National Heart Institute	Kuala Lumpur
Netherlands	Vrije Universiteit Amsterdam (VU)	Amsterdam
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	Erasmus MC	Rotterdam
Poland	Krakowski Szpital Specjalistyczny im Jana Pawla II	Kraków
Poland	Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ	Lublin
Puerto Rico	CardioPulmonary Research, PSC	Guaynabo
Singapore	National Heart Centre (NHC) Singapore	Singapore
Spain	Hosp. Univ. 12 de Octubre	Cardiologia
Spain	Hosp. Univ. Pta. de Hierro Majadahonda	Majadahonda
Spain	Hosp. Univ. Marques de Valdecilla	Santander
Sweden	Sahlgrenska Universitetsjukhuset	Goeteborg
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free 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 States	University of New Mexico	Albuquerque	New Mexico
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Maryland	Baltimore	Maryland
United States	Tufts Medical Center	Boston	Massachusetts
United States	Bay Area Cardiology Associates, P.A. - Brandon Office	Brandon	Florida
United States	Northwestern University	Chicago	Illinois
United States	University of Cinncinnati Physicans- UC Health Physicnas Office	Cincinnati	Ohio
United States	University of Missouri	Columbia	Missouri
United States	Houston Methodist Hospital	Houston	Texas
United States	University Of Iowa - Hospitals & Clinics	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Kentuckiana Pulmonary Associates	Louisville	Kentucky
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  China,  Germany,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  Puerto Rico,  Singapore,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to all Cause Death	Time to all cause death will be reported. All-cause death defined as deaths due to any cause.	Up to 6 years
Primary	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.	Up to 6 years
Secondary	Time to Death due to PAH	Time to death due to PAH will be reported.	Up to 6 years
Secondary	Time to First all-cause Hospitalization	Time to first all-cause hospitalization will be reported.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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).	Baseline up to 6 years
Secondary	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).	Baseline up to 6 years
Secondary	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).	Baseline up to 6 years
Secondary	Time to Worsening in WHO FC	Time to worsening in WHO FC will be reported.	Up to 6 months
Secondary	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.	Baseline up to 6 years
Secondary	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.	Up to 6 years
Secondary	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).	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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).	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	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.	Baseline up to 6 years
Secondary	PAH Symptoms and Impact using SYMPACT-CP Questionnaire	PAH symptoms and impact using SYMPACT-CP questionnaire will be reported.	Baseline up to 6 years