A Prospective Non-interventional Observational Study to Observe Long-term Treatment and Outcomes in Pulmonary Arterial Hypertension (PAH) Patients (TripleTRE-NIS)

A Prospective, Multicenter, International Non-interventional, Observational Cohort Study to Observe Long-term Treatment Patterns and Real-word Outcomes in PAH Group I Patients Previously Participating in TripleTRE - TripleTRE-NIS

The goal of this observational study is to learn about the long-term development and outcomes of different treatment patterns of patients who initially participated in the TripleTRE study.

The primary objective of this non-interventional follow-up study is to assess the long-term real-world clinical outcomes, including disease progression and survival rates, in patients who initially participated in and completed the randomized TripleTRE trial.

Planned observation duration per patient is a minimum of 3 years.

Study Overview

• Status: Enrolling by invitation
• Conditions: Pulmonary Arterial Hypertension

• Study Type: Observational
• Enrollment (Estimated): 110

Contacts and Locations

Study Locations

• Austria
  • Linz, Austria
    • Ordensklinikum Linz
  • Vienna, Austria
    • Medical University Vienna
• Czechia
  • Olomouc, Czechia
    • Fakultni nemocnice Olomouc
  • Praha, Czechia
    • Vseobecna fakultni nemocnice v Praze
• France
  • Paris, France
    • Hôpital Bicêtre-- Assistance Publique Hopitaux de Paris
  • Strasbourg, France
    • Hôpitaux Universitaires de Strasbourg
• Germany
  • Berlin, Germany
    • DRK Kliniken Berlin Westend
  • Dresden, Germany
    • University Hospital Carl Gustav Carus of Technical University Dresden
  • Greifswald, Germany
    • Universitätsmedizin Greifswald
• Hungary
  • Budapest, Hungary
    • Gottsegen National Cardiovascular lnstitute
  • Szeged, Hungary
    • Medical University of Szeged
• Italy
  • Rome, Italy
    • Sapienza University of Rome
• Poland
  • Kraków, Poland
    • John Paul II Hospital Krakow
  • Otwock, Poland
    • Fryderyk Chopin Hospital in European Health Centre Otwock
• Romania
  • Bucharest, Romania
    • Emergency Institute for Cardiovascular Diseases Prof. Dr. C.C.Iliescu
  • Târgu-Mureş, Romania
    • Emergency Clinical County Hospital of Targu Mures
• Spain
  • Barcelona, Spain
    • Hospital Clinic of Barcelona
  • Madrid, Spain
    • Hospital Ramon y Cajal

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients who participated in the TripleTRE study and who have not been lost to follow-up and have given a written informed consent for their participation in the NIS.

Description

Inclusion Criteria:

1. Patients previously participating in the randomized TripleTRE trial who are able and willing to provide a signed informed consent for study participation in NIS

Exclusion Criteria:

1. Lost to follow-up patients of TripleTRE study
2. Patients who discontinued all medicinal PAH treatments (e.g. after successful lung transplantation)
3. Patients who withdrew from the initial TripleTRE trial due to significant non-compliance with trial requirements (not adhering to therapy, not coming to hospital visits)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
TripleTRE NIS patients; all patients previously treated within the TripleTRE trial who are willing to participate in this NIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death or lung transplantation		up to year 3
Time to first clinical worsening	clinical worsening is defined as fulfilling on of the following criteria: PAH related death (including all deaths where PAH cannot be excluded as cause); Lung transplantation due to PAH; PAH-related hospitalization; Post baseline decrease in 6MWD by 15%; Post baseline worsening of WHO FC	up to year 3
Total number of clinical worsenings	clinical worsening is defined as fulfilling on of the following criteria: PAH related death (including all deaths where PAH cannot be excluded as cause); Lung transplantation due to PAH; PH-related hospitalization; Post baseline decrease in 6MWD by 15%; Post baseline worsening of WHO FC	up to year 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term change in 6MWD	6-Minute Walking Distance (6MWD) will be measured in meters	up to year 3
Long-term change in PAH treatment regimens	any change or addition of new PH medication including dosing in time	up to year 3
Long-term change in risk status	Risk status measured by simplified four-strata risk-assessment tool	up to year 3
Long-term change in WHO FC	World Health Organization Functional Class (WHO FC) is categorized from I (no symptoms) to IV (severe dyspnea and symptoms)	up to year 3
Long-term change in BDS	BDS - Borg Dyspnea Score, ranging from 0 (no exertion) to 10 (maximum)	up to year 3
Long-term change in NT-proBNP/BNP	NT-proBNP/BNP: N-terminal pro Brain Natriuretic Peptide	up to year 3
Long-term change in Pulmonary Vascular Resistance (PVR)	PVR to be measured in WU Parameter will be collected according to clinical routine	up to year 3
Long-term change in mean Pulmonary Arterial Pressure (mPAP)	mPAP to be measured in mmHg Parameter will be collected according to clinical routine	up to year 3
Long-term change in Right Atrial Pressure (RAP)	RAP to be measured in mmHg Parameter will be collected according to clinical routine	up to year 3
Long-term change in mean Right Atrial Pressure (mRAP)	mean Right Atrial Pressure (mRAP) to be measured in mmHg Parameter will be collected according to clinical routine	up to year 3
Long-term change in Cardiac Index (CI)	Cardiac index (CI) measured in liters per minute per square meter Parameter will be collected according to clinical routine	up to year 3
Long-term change in Cardiac Output (CO)	Cardiac output (CO) measured in liters per minute Parameter will be collected according to clinical routine	up to year 3
Long-term change in Pulmonary capillary wedge pressure (PCWP)	Pulmonary capillary wedge pressure (PCWP) measured in mmHg Parameter will be collected according to clinical routine	up to year 3
Long-term change in Stroke volume index (SVI)	Parameter will be collected according to clinical routine	up to year 3
Long-term change in RV-PA coupling	RV-PA coupling estimated by the ratio of tricuspid annular plane systolic excursion by pulmonary artery systolic pressure Parameter will be collected according to clinical routine	up to year 3
Long-term change in RV end-diastolic area (RVEDA)	RV end-diastolic area (RVEDA) measured in square centimeters Parameter will be collected according to clinical routine	up to year 3
Long-term change in RV end-systolic area (RVESA)	RV end-systolic area (RVESA) measured in square centimeters Parameter will be collected according to clinical routine	up to year 3
Long-term change in RV fractional area change (RVFAC)	RV fractional area change (RVFAC) calculated in % Parameter will be collected according to clinical routine	up to year 3
Long-term change in Right Atrium (RA) area	Right Atrium (RA) area in square centimeters Parameter will be collected according to clinical routine	up to year 3
Long-term change in Pericardial effusion	Pericardial effusion assessment will be done and rated as yes/no Parameter will be collected according to clinical routine	up to year 3
Long-term change in Right ventricular ejection fraction (RVEF)	Parameter will be collected according to clinical routine	up to year 3

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and seriousness of adverse events (AE) and adverse drug reactions (ADR)	This includes: Adverse events (S)AEs; Adverse drug reactions (S)ADRs related to any of PAH treatments; Adverse events related to underlying diagnosis, PAH	up to year 3
Long-term change in QoL using European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) questionnaire	The EQ-5D-5L questionnaire consists of 2 parts - the EQ-5D-5L descriptive system and the EQ Visual Analogue scale. The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking (or placing a cross) in the box against the most appropriate statement in each of the 5 dimensions. This decision results in a 1-digit number expressing the level selected for that dimension. The digits for 5 dimensions can be combined in a 5-digit number describing the respondent's health state. It should be noted that the numerals 1-5 have no arithmetic properties and should not be used as a cardinal score.	up to year 3
Long-term change in QoL using PAH-specific emPHasis-10 questionnaire	Emphasis meaning something of special importance or significance. Please translate using the most appropriate term. The PH in emPHasis represents the condition Pulmonary Hypertension. The number 10 refers to the number of items in the questionnaire. This questionnaire is designed to determine how Pulmonary Hypertension (PH) affects patient's life. It refers to how PH affects or the impact that PH has on the patient's life.	up to year 3

Collaborators and Investigators

• Sponsor: AOP Orphan Pharmaceuticals AG

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2024
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: May 29, 2024
• First Submitted That Met QC Criteria: June 4, 2024
• First Posted (Actual): June 6, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: TREV1-10P.NIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No