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

NCT03078907 | Completed Phase 4 Results FDA Drug

• 1 other identifier: AC-065A404
• Study Type: interventional
• Target: 108
• Locations: 10 countries
• Sites: 39

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

daily life; physical activity; actigraphy; PAH-SYMPACT

Outcome Measures

Primary Outcomes (10)

• Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes

  Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (as defined by Freedson '98 and Koster '16) and daily time spent in moderate-to-vigorous physical activity (MVPA) as defined by Freedson '98 were reported. These variables were assessed by actigraphy and were expressed in minutes. Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)

  Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (Freedson '98), daily time spent in moderate-to-vigorous physical activity (MVPA) (Freedson '98) and dailytime spent in NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in percentage (%). Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)

  Change from baseline to Week 24 of the DLPA activity parameter for total daily activities and NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in counts/minutes. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts

  Change from baseline to Week 24 of the DLPA activity parameters for volume of non-sedentary activity (Koster '16)were reported. These variables were assessed by actigraphy and were expressed in counts. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts

  Change from baseline to Week 24 of the DLPA activity parameters for number of steps during awake time were reported. These variables were assessed by actigraphy and were expressed in step counts. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute

  Change from baseline to Week 24 of the DLPA activity parameters for number of steps during awake time were reported. These variables were assessed by actigraphy and were expressed in step counts/minute. Positive change from baseline means improvement.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Total Sleep Time (TST)

  TST (in minutes) was assessed by actigraphy.

  Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

• Change From Baseline to Week 24 in Wake After Sleep Onset (WASO)

  WASO (in minutes) was assessed by actigraphy.

  Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

• Change From Baseline to Week 24 in Number of Awakenings

  Number of awakenings was assessed by actigraphy.

  Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

• Change From Baseline to Week 24 in Sleep Efficiency (SE)

  SE (in percentage) was assessed by actigraphy. Sleep efficiency was defined as the TST divided by the time in bed (minutes) multiplied by 100. TST was the duration in minutes including REM sleep plus NREM sleep during the time spent in bed.

  Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

Secondary Outcomes (5)

• Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score

  Baseline and Week 24

• Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)

  Baseline and Week 24

• Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)

  Baseline and Week 24

• Change From Baseline to Week 24 in Borg Dyspnea Score

  Baseline and Week 24

• Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)

  Baseline and Week 24

Study Arms (2)

Selexipag

EXPERIMENTAL

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.

Drug: Selexipag

Placebo

PLACEBO COMPARATOR

Regimen and titration scheme similar to those in the selexipag group

Drug: Placebo

Interventions

Selexipag DRUG

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

Also known as: ACT-293987, Uptravi

Selexipag

Placebo DRUG

Matching film coated tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• minute walk distance (6MWD) ≥ 100 m at screening.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (39)

LA Biomedical Research Institute

Torrance, California, 90502, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Kentuckiana Pulmonary Research Center

Louisville, Kentucky, 40202, United States

Location

Tufts Medical Center, Pulmonary/Critical Care & Sleep

Boston, Massachusetts, 02111, United States

Location

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

Omaha, Nebraska, 68198, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

UNC Pulmonary Speciality Clinic

Chapel Hill, North Carolina, 27599, United States

Location

Duke University School of Medicine, Duke Pulmonary Vascular Disease center

Durham, North Carolina, 27710, United States

Location

University of Cincinnati, Heart, Lung and Vascular Institute

Cincinnati, Ohio, 45267-0564, United States

Location

CCF- Akron General Medical Hospital

Cleveland, Ohio, 44307, United States

Location

Integris Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

University of Pennsylvania, Pulmonary Vascular Disease Program

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center, Care Medicine

Nashville, Tennessee, 37232-2650, United States

Location

Methodist Clinical Trials

San Antonio, Texas, 78229, United States

Location

University of Texas Health Science Center (San Antonio)

San Antonio, Texas, 78229, United States

Location

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

Innsbruck, 06020, Austria

Location

Krankenhaus der Elisabethinen, Servicestelle Klinische Studien

Linz, 4020, Austria

Location

Hôpital Bicêtre, ervice de Pneumologie et Réanimation respiratoire

Le Kremlin-Bicêtre, 94270, France

Location

CHRU de Lille - Hôpital Albert Calmette, Service de cardiologie

Lille, 59000, France

Location

Hospital Larrey CHU de Toulouse

Toulouse, 31059, France

Location

Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin

Cologne, 50937, Germany

Location

Universitätsklinikum Giessen

Giessen, 35392, Germany

Location

Universitätsklinikum Leipzig AöR, Abteilung Pneumologie

Leipzig, 04103, Germany

Location

Katholisches Klinikum Lünen/Werne GmbH, Haus E

Lünen, 44534, Germany

Location

Mater Misericordiae University Hospital

Dublin, D07 R2WY, Ireland

Location

Oslo University Hospital, dept of cardiology

Oslo, 0372, Norway

Location

Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia

Coimbra, 3000-075, Portugal

Location

Hospital Geral de Santo António-DEFI

Porto, 4099-001, Portugal

Location

Sahlgrenska University Hospital, Gothenburg

Gothenburg, 413 45, Sweden

Location

Skåne University Hospital, VO Hjärt och Lungmedicin

Lund, 221 85, Sweden

Location

Kantonsspital St. Gallen, Klinik für Pneumologie und Schlafmedizin

Sankt Gallen, 9007, Switzerland

Location

Universitaetsspital Zurich, Klinik für Pneumologie C HOER 11

Zurich, 8091, Switzerland

Location

Papworth Hospital, Pulmonary Vascular Disease Unit

Cambridge, Cb23 3RE, United Kingdom

Location

Golden Jubilee National Hospital, Scottish Pulmonary Vascular Unit

Clydebank, G81 4DY, United Kingdom

Location

The Royal Free Hospital, Cardiology Department

London, NW3 2QG, United Kingdom

Location

Royal Brompton Hospital, Hypertension

London, SW3 6NP, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Freeman Hospital, Cardiothoracic Department

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Hallamshire Hospital, Pulmonary Vascular Medicine

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40433632 DERIVED

• 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.

  PMID: 36089068 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Motor Activity

Interventions

selexipag

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Behavior

Limitations and Caveats

No hypothesis testing was planned for this exploratory study. Data for sleep outcome measures were not reported because the sleep episodes were not identified due to unexpected inaccuracy in automated sleep detection algorithm which resulted in missing/unreliable sleep data which would mislead the design of future trials and the interpretation of sleep results.

Results Point of Contact

• Title: Clinical Registry group
• Organization: Actelion Pharmaceuticals Ltd

clinical-trials-disclosure@its.jnj.com

844-434-4210

Study Officials

• Thomas Pfister

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 14, 2017
• Study Start: November 8, 2017
• Primary Completion: February 10, 2020
• Study Completion: February 10, 2020
• Last Updated: March 30, 2025
• Results First Posted: February 23, 2021

Record last verified: 2025-03

Locations

FR (3); CH (2); US (15); GB (7); SE (2); IE (1); DE (4); NO (1); PT (2); AU (2)