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 (SELECT)
Chronic Thromboembolic Pulmonary Hypertension
About this trial
This is an interventional treatment trial for Chronic Thromboembolic Pulmonary Hypertension focused on measuring CTEPH, selexipag
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
Sites / Locations
- University of California San Diego Medical Center
- University of Southern California, Keck School of Medicine
- University of Colorado - Anschutz Medical Campus
- Colorado Springs Pulmonary Consultants
- South Denver Cardiology Associates PC
- Mayo Clinic in Florida
- Piedmont Healthcare
- Emory University
- Northwestern University Feinberg School of Medicine
- University of Chicago Hospitals - Chicago
- Advocate Christ Medical Center
- University of Maryland
- University of Michigan
- Sparrow Clinical Research Institute
- Mayo Clinic
- Washington University in St. Louis
- University of Nebraska Medical Center
- St. Mary's Cardiology
- University of New Mexico Clinical & Translational Science Center
- Duke University Medical Center
- University of Cincinnati Medical Center
- Cleveland Clinic
- Temple University Hospital
- Allegheny
- University of Pittsburgh Medical Center
- University of Texas Southwestern Medical Center
- Houston Methodist Hospital
- Baylor Scott & White Research Institute at The Heart Hospital Baylor Plano
- Intermountain Medical Center
- University of Utah Cardiovascular Center
- Medical College of Wisconsin-Froedtert Hospital
- Aurora Saint Lukes Medical Center
- Sanatorio de la Trinidad Mitre
- Hospital Italiano de Buenos Aires
- Sanatorio Ramon Cereijo
- Instituto de Cardiología y Cirugía Cardiovascular - Fundación Favaloro
- Hospital General de Agudos Dr Cosme Argerich
- Hospital Britanico de Buenos Aires
- Centro Médico Dra. De Salvo
- Royal Adelaide Hospital
- Queensland Lung Transplant Service
- St Vincent's hospital
- Pulmonary Arterial Hypertension Clinic
- The Alfred Hospital
- Westmead Hospital
- Ordensklinikum Linz GmbH Elisabethinen
- Medical University Vienna
- ULB Hôpital Erasme
- UZ Leuven
- Universidade Federal De Minas Gerais - Hospital das Clínicas
- Instituto das Pequenas Missionárias de Maria Imaculada - Hospital Madre Teresa
- Fundacao para o Desenvolvimento Medico Hospitalar (UNESP Botucatu)
- Secretaria da Saude do Estado do Ceara - Hospital Doutor Carlos Alberto Studart Gomes
- Universidade Federal de Goias - Hospital das Clinicas da UFG
- Irmandade Santa Casa de Misericordia de Porto Alegre
- Hospital das Clinicas de Porto Alegre
- União Brasileira de Educação e Assistência-Hospital São Lucas da PUCRS
- Fundacao do ABC - Centro Universitario FMABC
- SPDM - Associacao Paulista para o Desenvolvimento da Medicina - Hospital Sao Paulo
- Hospital Das Clinicas Da Faculdade De Medicina Da USP
- UMHAT 'Heart and Brain Center for Excellence'
- National Cardiology Hospital
- University Multiprofile Hospital for Active Treatment- UMHAT Sveta Anna AD
- University Of Calgary - Peter Lougheed Centre
- Vancouver General Hospital
- London Health Sciences Centre - Victoria Hospital
- Jewish General Hospital
- Institut Universitaire De Cardiologie Et De Pneumologie De Québec
- Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College(PUMC)
- The First Affiliated Hospital of Guangzhou Medical University
- The General Hospital of Northern Theater Command
- Shengjing Hospital of China Medical University
- Shanxi Cardiovascular Hospital
- Tianjin Medical University General Hospital
- General University Hospital II.department of Internal Medicine-cardiology and angiology
- Århus Universitetshospital, Skejby, Hjertemedicinsk Afdeling B
- Rigshospitalet Kardiologisk Klinisk
- Universitätsklinikum Carl Gustav Carus Medizinische Klinik und Poliklinik 1-Pneumologie
- Universitätsklinikum Giessen Medizinische Klinik Und Poliklinik Ii, Pneumologie
- Universität Greifswald - Klinik Für Innere Medizin Bereich Pneumologie/Infektiologie
- Universitätsklinikum Hamburg-Eppendorf - Pneumologie
- Medizinische Hochschule Hannover Zentrum Innere Medizin Klinik für Pneumologie
- Thoraxklinik am Universitätsklinikum Heidelberg
- Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
- Universitätsklinikum Leipzig / Medizinischen Klinik und Poliklinik I, Abteilung für Pneumologie
- Klinikum Würzburg Mitte gGmbH Standort Missioklinik
- Semmelweis Egyetem,Pulmonológiai Klinika
- Gottsegen György Országos Kardiológiai Intézet, Felnőtt kardiológiai osztály
- Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
- Pecsi Tudomanyegyetem Klinikai Kozpont
- Szegedi Tudományegyetem, Általános Orvostudományi Kar, Családorvosi Intézet és rendelő
- Rabin Medical Center, Beilinson Campus
- The Chaim Sheba Medical Center
- Azienda Ospedaliera Policlinico S. Orsola-Malpighi
- Fondazione IRCCS Policlinico San Matteo
- Policlinico Umberto I
- Ospedale di Cattinara - Struttura complessa di Pneumologia
- Pusan National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- Seoul National University Hospital
- Hospital Pulau Pinang
- Hospital Serdang
- Institut Jantung Negara (National Heart Institute)
- Instituto Nacional de Cardiologia Dr. Ignacio Chavez
- CICUM San Miguel
- Unidad de Investigacion Clinica en Medicina S.C. (UDICEM)
- VUMC Amsterdam
- St. Antonius Ziekenhuis Nieuwegein
- Uniwersyteckie Centrum Kliniczne
- Krakowski Szpital Specjalistyczny im Jana Pawla II
- Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego SPZOZ
- NZOZ Europejskie Centrum Zdrowia Otwock
- Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
- Samodzielny Publiczny Szpital Kliniczny nr 2 PUM
- Warszawski Uniwersytet Medyczny, Szpital Kliniczny Dzieciątka Jezus
- Wojewodzki Szpital Specjalist, Osrodek Badawczo-Rozwojowy
- Hospital Garcia de Orta
- Hospitais da universidade de Coimbra
- Centro Hospitalar de Lisboa Norte
- Hospital Geral de Santo Antonio
- Irkutsk Regional Clinical Hospital
- Cardiovascular Pathology Research Institute of Siberian Branch of RAMS
- Moscow City Clinical Hospital #1 n.a. N.I.Pirogov
- Moscow City Clinical Hospital No.51
- National Medical Research Center of Cardiology of MoH of Russian Federation
- E.Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation
- National medical Research Center n.a. V.A.Almazov of MoH of Russian Federation
- Narodny ustav srdcovych a cievnych chorob
- Hosp. Clinic I Provincial de Barcelona
- Hosp. Univ. Vall D Hebron
- Hosp. Univ. 12 de Octubre
- Hosp. Univ. Marques de Valdecilla
- Hosp. Virgen Del Rocio
- Hosp. Univ. I Politecni La Fe
- Norrlands Universitetssjukhus
- Uppsala Akademiska Sjukhuset, Kardiologkliniken
- Universitatsspital Zurich
- Kaohsiung Veterans General Hospital
- China Medical University Hospital
- National Cheng Kung University Hospital
- National Taiwan University Hospital
- Ramathibodi Hospital, Mahidol University
- Srinagarind Hospital, Khon Kaen University
- Hacettepe University Medical Faculty
- Ankara University Medical Faculty
- Istanbul University Istanbul Medical Faculty
- Istanbul University Cerrahpasa Medical Faculty
- Marmara University Medical Faculty
- Ege University Medical Faculty
- Kartal Kosuyolu Yuksek Ihtisas Egitim Ve Arastirma Hastanesi
- CE 'Dnipropetrovsk Regional Clinical Center of Cardiology and Cardiosurgery'
- SI National Scientific Center Institute of Cardiology of M.D. Strazhesko of NAMS of Ukraine
- SI 'National Institute of Phtisiology and Pulmonology n.a. F.G. Yanovsky of NAMS of Ukraine'
- Lviv Regional Clinical Hospital
- Papworth Hospital NHS Trust
- National Waiting Times Centre Board Golden Jubilee National Hospital
- Royal Free Hospital
- Royal Brompton Hospital
- Hammersmith Hospital
- Sheffield Teaching Hospitals NHS Foundation Trust Royal Hallamshire Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Placebo Comparator
Experimental
Selexipag DB
Placebo DB
Selexipag OL
During the double blind treatment period, participants in this group will receive selexipag. Each participant will start with one oral tablet of selexipag 200 µg in the evening of Day 1 and will continue with 200 µg twice daily (b.i.d.) on Day 2. If this dose is well-tolerated, selexipag is up-titrated with weekly increments of 200 µg until reaching the individual maximal tolerated dose (iMTD) in the range of 200 to 1600 µg b.i.d. The up-titration period up to Week 12 is followed by a stable maintenance treatment period from Week 12 to Week 26, at the iMTD. After Week 26, further up-titration can be allowed (but not above 1600 µg b.i.d.).
During the double-blind treatment period, participants in this group will receive the oral matching placebo, twice daily. A (mock) up-titration scheme will be followed.
All participants who completed the double-blind treatment period, whether they received placebo or selexipag during the double-blind period, will receive selexipag during the open-label extension period, using the same up-titration schedule as in the double-blind period.