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

Pulmonary Arterial Hypertension Clinical Trial

— TRACE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03078907
• Other study ID #: AC-065A404
• Status: Completed
• Phase: Phase 4
• Start date: November 8, 2017
• Est. completion date: February 10, 2020

Study information

• Verified date: February 2021
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: February 10, 2020
• Est. primary completion date: February 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Selexipag
Film-coated tablets for oral use; one tablet (200 mcg) to eight tablets (1600 mcg) are administered depending on the individual tolerability.
• Placebo
Matching film coated tablets

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck (MUI), Abt. für Pneumologie, Haus 2	Innsbruck
Austria	Krankenhaus der Elisabethinen, Servicestelle Klinische Studien	Linz
France	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
Germany	Universitätsklinikum Giessen	Giessen
Germany	Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin	Köln
Germany	Universitätsklinikum Leipzig AöR, Abteilung Pneumologie	Leipzig
Germany	Katholisches Klinikum Lünen/Werne GmbH, Haus E	Lünen
Ireland	Mater Misericordiae University Hospital	Dublin
Norway	Oslo University Hospital, dept of cardiology	Oslo
Portugal	Centro Hospitalar e Universitário de Coimbra, Serviço de Cardiologia	Coimbra
Portugal	Hospital Geral de Santo António-DEFI	Porto
Sweden	Sahlgrenska University Hospital, Gothenburg	Gothenburg
Sweden	Skåne University Hospital, VO Hjärt och Lungmedicin	Lund
Switzerland	Kantonsspital St. Gallen, Klinik für Pneumologie und Schlafmedizin	St. Gallen
Switzerland	Universitaetsspital Zurich, Klinik für Pneumologie C HOER 11	Zurich
United Kingdom	Papworth Hospital, Pulmonary Vascular Disease Unit	Cambridge
United Kingdom	Golden Jubilee National Hospital, Scottish Pulmonary Vascular Unit	Clydebank
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Brompton Hospital, Hypertension	London
United Kingdom	The Royal Free Hospital, Cardiology Department	London
United Kingdom	Freeman Hospital, Cardiothoracic Department	Newcastle Upon Tyne
United Kingdom	Royal Hallamshire Hospital, Pulmonary Vascular Medicine	Sheffield
United States	Northside Hospital	Atlanta	Georgia
United States	Tufts Medical Center, Pulmonary/Critical Care & Sleep	Boston	Massachusetts
United States	UNC Pulmonary Speciality Clinic	Chapel Hill	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	Duke University School of Medicine, Duke Pulmonary Vascular Disease center	Durham	North Carolina
United States	Kentuckiana Pulmonary Research Center	Louisville	Kentucky
United States	NYU Winthrop Hospital	Mineola	New York
United States	Vanderbilt University Medical Center, Care Medicine	Nashville	Tennessee
United States	Integris Baptist Medical Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center, Pulmonary, Critical Care & Sleep Medicine Division	Omaha	Nebraska
United States	University of Pennsylvania, Pulmonary Vascular Disease Program	Philadelphia	Pennsylvania
United States	Methodist Clinical Trials	San Antonio	Texas
United States	University of Texas Health Science Center (San Antonio)	San Antonio	Texas
United States	LA Biomedical Research Institute	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score	PAH-SYMPACT has 2 main parts: symptoms (cardiopulmonary and cardiovascular) and impact (physical impacts and cognitive/emotional). The symptom part is a questionnaire completed daily for 7 consecutive days and contains 11 items. The impact part has a 7-day recall period and is completed on 7th day of symptoms questionnaire data collection period. It contains 11 items pertaining to impact of PAH. The average Cardiopulmonary Symptoms and cardiovascular symptoms domain scores are determined based on daily scores of 6 and 5 items, respectively, reported on a 5-point Likert scale with score range from 0=best to 4=worst. The Physical impacts and Cognitive/emotional domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 = "not at all"/"with no difficulty at all" and value 4 = "very much"/"extremely"/ "not able at all". Mean value on each of 7-day period was calculated for each specific domain score and corresponding mean change from baseline was reported.	Baseline and Week 24
Secondary	Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)	The WHO FC of pulmonary hypertension is a physical activity rating scale as follows: Class I (No limitation of physical activity); Class II (Slight limitation of physical activity); Class III (Marked limitation of physical activity); and Class IV (Inability to carry out any physical activity without symptoms). The change from baseline in WHO FC was classified into "Improved", "No change" and "Worsened" compared to baseline. Deterioration, No Change, and Improvement are based on shift of risk category (I, II, III, IV) from baseline in WHO Functional Class.	Baseline and Week 24
Secondary	Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)	The 6MWD was the total distance walked during 6 minutes. Mean change from baseline (distance walked at Week 24 minus distance walked at baseline) was reported.	Baseline and Week 24
Secondary	Change From Baseline to Week 24 in Borg Dyspnea Score	The Borg dyspneas score was a self-rating scale to evaluate the severity of dyspnea (from 0 "no shortness of breath at all" to 10 "very, very severe / maximal") shortness of breath. It was completed immediately after the 6-minute walk test at Week 24 and at baseline. Mean change from baseline in scoring was reported.	Baseline and Week 24
Secondary	Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)	Change from baseline to Week 24 in NT-pro BNP levels was reported. The negative change from baseline means improvement.	Baseline and Week 24