Clinical trial NCT03689244: A Study to Find Out if Selexipag is Effective and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension When the Disease is Inoperable or Persistent/Recurrent After Surgery and/or Interventional Treatment
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Group-sequential, Adaptive, Phase 3 Study With Open-label Extension Period to Assess the Efficacy and Safety of Selexipag as an add-on to Standard of Care Therapy in Subjects With Inoperable or Persistent/Recurrent After Surgical and/or Interventional Treatment Chronic Thromboembolic Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Keywords: CTEPH
selexipag
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2018-09-28
Enrollment: 128
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Selexipag is available in many countries for the treatment of pulmonary arterial hypertension (PAH). Due to the similarities between PAH and chronic thromboembolic pulmonary hypertension (CTEPH) and the observed efficacy of other PAH medicines in CTEPH, it is believed that selexipag could benefit to patients with CTEPH. This study aims to assess the efficacy and safety of selexipag in participants with inoperable or persistent/recurrent CTEPH.

Detailed description: Participants will be recruited in two sequential cohorts: approximately the first 90 randomized participants will undergo a right heart catheterization (RHC) (and left heart catheterization LHC, if needed) with measurement of pulmonary vascular resistance (PVR) at Week 20 and will constitute the hemodynamic cohort; the remaining participants will constitute the non-hemodynamic cohort; who do not require a post-baseline hemodynamic assessment. They will undergo the same overall study assessments as the hemodynamic cohort excepted for RHC at Week 20.

Eligibility criteria: Main Inclusion Criteria:

* Signed and dated informed consent form
* Male and female participants from greater than or equal to (\>) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) and less then or equal to (\<=85) years old at Screening (Visit 1)
* With established diagnosis of inoperable CTEPH (i.e., technically non-operable) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA), as confirmed by the corresponding adjudication committee
* With pulmonary hypertension (PH) in WHO FC I-IV.
* Participant able to perform the 6-minute walk test (6MWT) with a minimum distance of 100 m and a maximum distance of 450 m at screening visit.
* Women of childbearing potential must have a negative pregnancy test at screening and randomization and must agree to undertake monthly urine pregnancy tests, and to use a reliable method of birth control from screening visit up to at least 30 days after study treatment discontinuation. If a hormonal contraceptive is chosen it must be taken for at least 1 month prior to randomization.

Main Exclusion Criteria:

* Planned or current treatment with another investigational treatment up to 3 months prior to randomization.
* Any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease.
* Known concomitant life-threatening disease with a life expectancy \< 12 months.
* Planned balloon pulmonary angioplasty within 26 weeks after randomization.
* Change in dose or initiation of new PH-specific therapy within 90 days prior to the baseline RHC (and LHC, if needed) qualifying for enrollment for the hemodynamic cohort and within 90 days prior to randomization (Visit 2) for the non-hemodynamic cohort
* Treatment with prostacyclin (epoprostenol), prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e., selexipag) within 90 days prior to randomization (visit 2) except those given at vasodilator testing during RHC
* Change in dose or initiation of new diuretics and/or calcium channel blockers within 1 week prior to baseline RHC (and LHC, if needed)
* Any co-morbid condition that may influence the ability to perform a reliable and reproducible 6MWT, including use of walking aids (cane, walker, etc).
* Any other criteria as per selexipag Summary of Product Characteristics (SmPC).
* Exclusion criteria related to comorbidities: severe coronary heart disease or unstable angina as assessed by the investigator; mocardial infarction within the last 6 months prior to or during Screening; decompensated cardiac failure if not under close supervision; severe arrhythmias as assessed by the investigator; cerebrovascular events (example transient ischemic attack, stroke) within the last 3 months prior to or during screening; congenital or acquired valvular defects with clinically relevant myocardial function disorders not related to pulmonary hypertension. (PH); known or suspicion of pulmonary veno-occlusive disease

Primary outcomes:
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 20
timeFrame: Baseline (Day 1, pre-dose), within 2 to 5 hours post-dose on Week 20
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California, Keck School of Medicine
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Colorado Springs
country: United States
facility: Colorado Springs Pulmonary Consultants
state: Colorado
city: Littleton
country: United States
facility: South Denver Cardiology Associates PC
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Hospitals - Chicago
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Reno
country: United States
facility: St. Mary's Cardiology
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Clinical & Translational Science Center
state: New Mexico
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White Research Institute at The Heart Hospital Baylor Plano
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Cardiovascular Center
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Froedtert Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Saint Lukes Medical Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Sanatorio de la Trinidad Mitre
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Caba
country: Argentina
facility: Sanatorio Ramon Cereijo
city: Caba
country: Argentina
facility: Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro
city: Caba
country: Argentina
facility: Hospital General de Agudos Dr Cosme Argerich
city: Caba
country: Argentina
facility: Hospital Britanico de Buenos Aires
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Centro Médico Dra. De Salvo
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Chermside
country: Australia
facility: Queensland Lung Transplant Service
city: Darlinghurst
country: Australia
facility: St Vincent's hospital
city: Hobart
country: Australia
facility: Pulmonary Arterial Hypertension Clinic
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Westmead
country: Australia
facility: Westmead Hospital
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Vienna
country: Austria
facility: Medical University Vienna
city: Brussels
country: Belgium
facility: ULB Hôpital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven
city: Belo Horizonte
country: Brazil
facility: Universidade Federal De Minas Gerais - Hospital das Clínicas
city: Belo Horizonte
country: Brazil
facility: Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
city: Botucatu
country: Brazil
facility: Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
city: Fortaleza
country: Brazil
facility: Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
city: Goiania
country: Brazil
facility: Universidade Federal de Goias - Hospital das Clinicas da UFG
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
city: Santo Andre
country: Brazil
facility: Fundacao do ABC - Centro Universitario FMABC
city: Sao Paulo
country: Brazil
facility: SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Das Clinicas Da Faculdade De Medicina Da USP
city: Pleven
country: Bulgaria
facility: UMHAT 'Heart and Brain Center for Excellence'
city: Sofia
country: Bulgaria
facility: National Cardiology Hospital
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
city: Calgary
country: Canada
facility: University Of Calgary - Peter Lougheed Centre
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec
country: Canada
facility: Institut Universitaire De Cardiologie Et De Pneumologie De Québec
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College(PUMC)
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
city: Shenyang
country: China
facility: The General Hospital of Northern Theater Command
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
city: Taiyuan
country: China
facility: Shanxi Cardiovascular Hospital
city: Tian Jin
country: China
facility: Tianjin Medical University General Hospital
city: Praha 2
country: Czechia
facility: General University Hospital II.department of Internal Medicine-cardiology and angiology
city: Arhus
country: Denmark
facility: Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
city: Copenhagen
country: Denmark
facility: Rigshospitalet Kardiologisk Klinisk
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
city: Giessen
country: Germany
facility: Universitätsklinikum Giessen Medizinische Klinik Und Poliklinik Ii, Pneumologie
city: Greifswald
country: Germany
facility: Universität Greifswald - Klinik Für Innere Medizin Bereich Pneumologie/Infektiologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf - Pneumologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitatsklinikum Heidelberg
city: Homburg/Saar
country: Germany
facility: Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig Medizinischen Klinik und Poliklinik I, Abteilung für Pneumologie
city: Würzburg
country: Germany
facility: Klinikum Würzburg Mitte gGmbH Standort Missioklinik
city: Budapest
country: Hungary
facility: Semmelweis Egyetem,Pulmonológiai Klinika
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem Klinikai Kozpont
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
city: Petah Tikva
country: Israel
facility: Rabin Medical Center Beilinson Campus
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliera Policlinico S. Orsola-Malpighi
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Trieste
country: Italy
facility: Ospedale di Cattinara - Struttura complessa di Pneumologia
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
city: Kajang
country: Malaysia
facility: Hospital Serdang
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara (National Heart Institute)
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Dr. Ignacio Chavez
city: Guadalajara
country: Mexico
facility: CICUM San Miguel
city: Monterrey
country: Mexico
facility: Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
city: Amsterdam
country: Netherlands
facility: VUMC Amsterdam
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Nieuwegein
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Krakow
country: Poland
facility: Krakowski Szpital Specjalistyczny im Jana Pawla II
city: Lublin
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
city: Otwock
country: Poland
facility: NZOZ Europejskie Centrum Zdrowia Otwock
city: Poznań
country: Poland
facility: Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
city: Warszawa
country: Poland
facility: Warszawski Uniwersytet Medyczny, Szpital Kliniczny Dzieciątka Jezus
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Coimbra
country: Portugal
facility: Hospitais da universidade de Coimbra
city: Lisbon
country: Portugal
facility: Centro Hospitalar de Lisboa Norte
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio
city: Irkutsk
country: Russian Federation
facility: Irkutsk Regional Clinical Hospital
city: Kemerovo
country: Russian Federation
facility: Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
city: Moscow
country: Russian Federation
facility: Moscow City Clinical Hospital No.51
city: Moscow
country: Russian Federation
facility: National Medical Research Center of Cardiology of MoH of Russian Federation
city: Novosibirsk
country: Russian Federation
facility: E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
city: Bratislava
country: Slovakia
facility: Narodny ustav srdcovych a cievnych chorob
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp. Univ. Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Sjukhuset, Kardiologkliniken
city: Zürich
country: Switzerland
facility: Universitatsspital Zurich
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital Mahidol University
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital, Khon Kaen University
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Istanbul Medical Faculty
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Kartal Istanbul
country: Turkey
facility: Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
city: Dnipro
country: Ukraine
facility: CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
city: Kyiv
country: Ukraine
facility: SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
city: Kyiv
country: Ukraine
facility: SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Trust
city: Glasgow
country: United Kingdom
facility: National Waiting Times Centre Board Golden Jubilee National Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Study officials:
affiliation: Actelion
name: Julian Borissoff, MD, PhD
role: STUDY_DIRECTOR
References: