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Rationale and Design of TRACE: A Double-Blind, Placebo-Controlled Phase 4 Study in Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Physical Activity, Patient-Reported Symptoms and

Ioana Preston


Robert Frantz


Anna Hemnes


Stephan Rosenkranz

Hall Skaara

Thomas Pfister

Marc Humbert


Luke Howard

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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1058

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Rationale and Design of TRACE: A Double-Blind, Placebo-Controlled Phase 4 Study in Pulmonary Arterial Hypertension to Assess the Effect of Selexipag on Physical Activity, Patient-Reported Symptoms and Their Impact, in Daily Life

Background

Impaired daily life physical activity (DLPA) is associated with poor quality of life and adverse cardiovascular outcomes. Recent studies have shown that DLPA is reduced in patients with pulmonary arterial hypertension (PAH) and associated with worse outcomes, indicating the importance of monitoring DLPA in PAH. In addition, patient-reported outcomes (PROs) are increasingly recognized tools of quality of life assessment. Selexipag is an oral IP prostacyclin receptor agonist, indicated for the treatment of PAH to delay disease progression and reduce the risk of hospitalization. The objective of TRACE is to evaluate the effect of selexipag on DLPA and on patient-reported disease symptoms in PAH. This exploratory study will help to better understand the validity and usefulness of patient-centric elements as novel endpoints in future clinical trials in PAH.

Methods

This ongoing multi-center, double-blind, randomized, exploratory Phase 4 study randomizes (1:1) 100 patients to receive selexipag or placebo for 24 weeks. Eligible PAH patients are 18–75 years, in World Health Organization functional class (WHO FC) II or III, with a 6-minute walk distance (6MWD) ≥100 m, and on stable treatment with an endothelin receptor antagonist alone or in combination with a phosphodiesterase-5 inhibitor or soluble guanylate cyclase stimulator. DLPA is measured by the wrist-worn accelerometer ActiGraph GT9X Link, day and night during a 14 day baseline period and throughout the 24-week treatment period (Figure). Daily data upload on a provided smartphone allows wear-time monitoring. Patients remain blinded to their activity levels and sleep parameters until the end of study. PAH symptoms and their impact are assessed by completing the PAH-SYMPACT® questionnaire on the smartphone. The PAH-SYMPACT® questionnaire is the first PAH-specific PRO instrument developed and validated according to the FDA guidance. PAH-SYMPACT® is completed during three 7-day periods during the baseline period, and at weeks 15 and 23.

Results

The primary endpoint is change from baseline to week 24 in actigraphy-assessed DLPA, as measured by: daily time spent in non-sedentary activity, total DLPA per day, total sleep time, wake time after sleep onset, number of awakenings and sleep efficiency. Secondary endpoints include change in score from baseline in cardiovascular symptoms, cardiopulmonary symptoms, physical impact and cognitive/emotional impact domains of PAH-SYMPACT®, change in WHO FC, 6MWD, Borg dyspnea index and NT-proBNP. Safety and tolerability of selexipag are monitored.

Conclusions

TRACE is the first international, multi-center, randomized PAH study designed to utilize actigraphy combined with PRO to assess response to treatment.

 

Study design