Clinical trial NCT03078907: Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
Official title: A Multi-center, Double-blind, Placebo-controlled Phase 4 Study in Patients With Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Daily Life Physical Activity and Patient's Self-reported Symptoms and Their Impacts
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Arterial Hypertension
Keywords: daily life
physical activity
actigraphy
PAH-SYMPACT
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-03-14
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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

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.

Primary outcomes:
measure: Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Total Sleep Time (TST)
timeFrame: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
measure: Change From Baseline to Week 24 in Wake After Sleep Onset (WASO)
timeFrame: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
measure: Change From Baseline to Week 24 in Number of Awakenings
timeFrame: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
measure: Change From Baseline to Week 24 in Sleep Efficiency (SE)
timeFrame: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)
Secondary outcomes:
measure: Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score
timeFrame: Baseline and Week 24
measure: Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in Borg Dyspnea Score
timeFrame: Baseline and Week 24
measure: Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Torrance
country: United States
facility: LA Biomedical Research Institute
state: California
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Research Center
state: Kentucky
city: Boston
country: United States
facility: Tufts Medical Center, Pulmonary/Critical Care & Sleep
state: Massachusetts
city: Omaha
country: United States
facility: University of Nebraska Medical Center, Pulmonary, Critical Care & Sleep Medicine Division
state: Nebraska
city: Mineola
country: United States
facility: NYU Winthrop Hospital
state: New York
city: Chapel Hill
country: United States
facility: UNC Pulmonary Speciality Clinic
state: North Carolina
city: Durham
country: United States
facility: Duke University School of Medicine, Duke Pulmonary Vascular Disease center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati, Heart, Lung and Vascular Institute
state: Ohio
city: Cleveland
country: United States
facility: CCF- Akron General Medical Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania, Pulmonary Vascular Disease Program
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Care Medicine
state: Tennessee
city: San Antonio
country: United States
facility: Methodist Clinical Trials
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center (San Antonio)
state: Texas
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck (MUI), Abt. für Pneumologie, Haus 2
city: Linz
country: Austria
facility: Krankenhaus der Elisabethinen, Servicestelle Klinische Studien
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre, ervice de Pneumologie et Réanimation respiratoire
city: Lille
country: France
facility: CHRU de Lille - Hôpital Albert Calmette, Service de cardiologie
city: Toulouse
country: France
facility: Hospital Larrey CHU de Toulouse
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen
city: Köln
country: Germany
facility: Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR, Abteilung Pneumologie
city: Lünen
country: Germany
facility: Katholisches Klinikum Lünen/Werne GmbH, Haus E
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, dept of cardiology
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia
city: Porto
country: Portugal
facility: Hospital Geral de Santo António-DEFI
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital, Gothenburg
city: Lund
country: Sweden
facility: Skåne University Hospital, VO Hjärt och Lungmedicin
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen, Klinik für Pneumologie und Schlafmedizin
city: Zurich
country: Switzerland
facility: Universitaetsspital Zurich, Klinik für Pneumologie C HOER 11
city: Cambridge
country: United Kingdom
facility: Papworth Hospital, Pulmonary Vascular Disease Unit
city: Clydebank
country: United Kingdom
facility: Golden Jubilee National Hospital, Scottish Pulmonary Vascular Unit
city: London
country: United Kingdom
facility: The Royal Free Hospital, Cardiology Department
city: London
country: United Kingdom
facility: Royal Brompton Hospital, Hypertension
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital, Cardiothoracic Department
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital, Pulmonary Vascular Medicine
Study officials:
affiliation: Actelion
name: Thomas Pfister
role: STUDY_DIRECTOR
References:
citation: 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.