Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.

NCT ID: NCT03078907

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-08
• Study Completion Date: 2020-02-10

Brief Summary

The primary objective of this study is to evaluate the effect of selexipag on the physical activity of patients with pulmonary arterial hypertension (PAH) in their daily life, by using a wearable wrist device (actigraph). The actigraph will collect data on daily life physical activity in the patient's real environment. In addition, the PAH symptoms and their impacts will be assessed by using an electronic patient reported outcome measure in the patient's real environment. Patients will be assigned randomly to either selexipag or placebo.

Detailed Description

This study is designed as exploratory with the purpose to generate hypotheses on new endpoints

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Selexipag

Selexipag is up-titrated from Day 1 to Week 12 to the individualized highest tolerated dose (HTD), which can range from 200 mcg b.i.d. to 1600 mcg b.i.d., in 200 mcg steps starting with 200 mcg b.i.d. Then, the dose is increased in increments of 200 mcg b.i.d., usually at weekly intervals, depending on the dose tolerability. Up-titration is followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Group Type: EXPERIMENTAL

Selexipag

Intervention Type: DRUG

Film-coated tablets for oral use; one tablet (200 mcg) to eight tablets (1600 mcg) are administered depending on the individual tolerability.

Placebo

Regimen and titration scheme similar to those in the selexipag group

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching film coated tablets

Interventions

Selexipag

Film-coated tablets for oral use; one tablet (200 mcg) to eight tablets (1600 mcg) are administered depending on the individual tolerability.

Intervention Type: DRUG

Placebo

Matching film coated tablets

Intervention Type: DRUG

Other Intervention Names

ACT-293987; Uptravi

Eligibility Criteria

Inclusion Criteria

• Male or female between 18 and 75 years old inclusive.
• Women of childbearing potential must have a negative serum pregnancy test at planned visits and use an acceptable method of birth control from screening up to 30 days after study treatment discontinuation.
• Symptomatic pulmonary arterial hypertension (PAH) belonging to one of the following subgroups only:

• Idiopathic
• Heritable
• Drug or toxin induced
• Associated with one of the following: connective tissue disease; HIV infection; corrected simple congenital heart disease.
• With the following hemodynamic characteristics assessed by right heart catheterization (RHC) prior to randomization:

• Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
• Pulmonary vascular resistance (PVR) ≥ 240 dyn•sec/cm5 (or 3 Wood Units)
• Pulmonary artery wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤ 15 mmHg.
• Treatment with an endothelin receptor antagonist (ERA) for at least 90 days and on a stable dose for 30 days prior to randomization.
• If an ERA is given in combination with a phosphodiesterase-5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator, these treatments must be ongoing for at least 90 days and on a stable dose for 30 days prior to randomization.
• WHO functional class (FC) II or III at randomization
• 6-minute walk distance (6MWD) ≥ 100 m at screening.
• Ability to walk without a walking aid.
• Valid baseline data for daily life physical activity (DLPA) and PAH-SYMPACT®.

Exclusion Criteria

• Patients on a PAH-specific monotherapy targeting the nitric oxide pathway (i.e. PDE-5 inhibitor or sGC stimulator).
• Patients treated with prostacyclin, prostacyclin analog or selexipag within 3 months prior to screening.
• Any hospitalization during the last 30 days prior to screening.
• Severe coronary heart disease or unstable angina.
• Documented severe hepatic impairment or severe renal insufficiency at screening.
• Participation in a cardio-pulmonary rehabilitation program based on exercise training within 8 weeks prior to screening
• Any factor or condition likely to affect full participation in the study or compliance with the protocol (such as adherence to protocol mandated procedures), as judged by the investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Pfister

Role: STUDY_DIRECTOR

Actelion

Locations

LA Biomedical Research Institute

Torrance, California, United States

Northside Hospital

Atlanta, Georgia, United States

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, United States

Tufts Medical Center, Pulmonary/Critical Care & Sleep

Boston, Massachusetts, United States

University of Nebraska Medical Center, Pulmonary, Critical Care & Sleep Medicine Division

Omaha, Nebraska, United States

NYU Winthrop Hospital

Mineola, New York, United States

UNC Pulmonary Speciality Clinic

Chapel Hill, North Carolina, United States

Duke University School of Medicine, Duke Pulmonary Vascular Disease center

Durham, North Carolina, United States

University of Cincinnati, Heart, Lung and Vascular Institute

Cincinnati, Ohio, United States

CCF- Akron General Medical Hospital

Cleveland, Ohio, United States

Integris Baptist Medical Center

Oklahoma City, Oklahoma, United States

University of Pennsylvania, Pulmonary Vascular Disease Program

Philadelphia, Pennsylvania, United States

Vanderbilt University Medical Center, Care Medicine

Nashville, Tennessee, United States

Methodist Clinical Trials

San Antonio, Texas, United States

University of Texas Health Science Center (San Antonio)

San Antonio, Texas, United States

Medizinische Universität Innsbruck (MUI), Abt. für Pneumologie, Haus 2

Innsbruck, , Austria

Krankenhaus der Elisabethinen, Servicestelle Klinische Studien

Linz, , Austria

Hôpital Bicêtre, ervice de Pneumologie et Réanimation respiratoire

Le Kremlin-Bicêtre, , France

CHRU de Lille - Hôpital Albert Calmette, Service de cardiologie

Lille, , France

Hospital Larrey CHU de Toulouse

Toulouse, , France

Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin

Cologne, , Germany

Universitätsklinikum Giessen

Giessen, , Germany

Universitätsklinikum Leipzig AöR, Abteilung Pneumologie

Leipzig, , Germany

Katholisches Klinikum Lünen/Werne GmbH, Haus E

Lünen, , Germany

Mater Misericordiae University Hospital

Dublin, , Ireland

Oslo University Hospital, dept of cardiology

Oslo, , Norway

Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia

Coimbra, , Portugal

Hospital Geral de Santo António-DEFI

Porto, , Portugal

Sahlgrenska University Hospital, Gothenburg

Gothenburg, , Sweden

Skåne University Hospital, VO Hjärt och Lungmedicin

Lund, , Sweden

Kantonsspital St. Gallen, Klinik für Pneumologie und Schlafmedizin

Sankt Gallen, , Switzerland

Universitaetsspital Zurich, Klinik für Pneumologie C HOER 11

Zurich, , Switzerland

Papworth Hospital, Pulmonary Vascular Disease Unit

Cambridge, , United Kingdom

Golden Jubilee National Hospital, Scottish Pulmonary Vascular Unit

Clydebank, , United Kingdom

The Royal Free Hospital, Cardiology Department

London, , United Kingdom

Royal Brompton Hospital, Hypertension

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Freeman Hospital, Cardiothoracic Department

Newcastle upon Tyne, , United Kingdom

Royal Hallamshire Hospital, Pulmonary Vascular Medicine

Sheffield, , United Kingdom

Countries

United States; Austria; France; Germany; Ireland; Norway; Portugal; Sweden; Switzerland; United Kingdom

References

Rehman RZU, Parisi F, Ashraf N, Chatterjee M, Frantz RP, Hemnes AR, Manyakov NV, Carrasco-Zevallos OM, Yardibi T, Selej M, Mansi T, Dunnmon P, Kaliukhovich DA. Characteristics of Daily Walking Bouts as Valid and Reliable Indicators of Exercise Capacity in Pulmonary Arterial Hypertension: Insights From the Randomized Controlled Study With Selexipag (TRACE). Pulm Circ. 2025 May 26;15(2):e70097. doi: 10.1002/pul2.70097. eCollection 2025 Apr.

Reference Type: DERIVED

PMID: 40433632 (View on PubMed)

Howard LS, Rosenkranz S, Frantz RP, Hemnes AR, Pfister T, Hsu Schmitz SF, Skara H, Humbert M, Preston IR. Assessing Daily Life Physical Activity by Actigraphy in Pulmonary Arterial Hypertension: Insights From the Randomized Controlled Study With Selexipag (TRACE). Chest. 2023 Feb;163(2):407-418. doi: 10.1016/j.chest.2022.08.2231. Epub 2022 Sep 8.

Reference Type: DERIVED

PMID: 36089068 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-065A404

Identifier Type: -

Identifier Source: org_study_id