Clinical trial NCT00660179: Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Event-driven, Phase III Study to Assess the Effects of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Arterial Hypertension
Keywords: pulmonary arterial hypertension SERAPHIN
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2008-04-17
Enrollment: 742
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The AC-055-302/SERAPHIN study will be an event-driven Phase III study, comparing two different doses of macitentan (ACT-064992) (3 and 10 mg) vs placebo in patients with symptomatic PAH. The main study objective is to demonstrate that macitentan (ACT-064992) prolongs time to the first morbidity or mortality event, and to evaluate the benefit/risk profile of macitentan (ACT-064992) in the treatment of patients with symptomatic PAH.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent prior to initiation of any study mandated procedure.
2. Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV.
3. Patients with the following types of pulmonary arterial hypertension (PAH) belonging to groups 1.1 to 1.3 of the Venice classification:

   * Idiopathic (IPAH);
   * Familial (FPAH); or
   * Related to:

     * Collagen vascular disease;
     * Simple, congenital systemic-to-pulmonary shunts at least 1 year post surgical repair;
     * Human immunodeficiency virus (HIV) infection; or
     * Drugs and toxins.
4. PAH diagnosis confirmed by hemodynamic evaluation performed prior to randomization and showing all of the following:

   * Mean pulmonary artery pressure (mPAP) \> 25 mmHg at rest;
   * Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) \< 15 mmHg; and
   * Pulmonary vascular resistance (PVR) at rest \>= 320 dyn×sec/cm\^5.
5. 6-minute walk distance (6MWD) \>= 50 m.
6. Men or women \> 12 years of age (women of childbearing potential must have a negative pre-treatment serum pregnancy test and must use a reliable method of contraception).

Exclusion Criteria:

1. PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy.
2. PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected.
3. PAH associated with significant venous or capillary involvement (PCWP \> 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis.
4. Persistent pulmonary hypertension of the newborn.
5. Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification.
6. Moderate to severe obstructive lung disease: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) \< 70% and FEV1 \< 65% of predicted value after bronchodilator administration.
7. Moderate to severe restrictive lung disease: total lung capacity (TLC) \< 60% of predicted value.
8. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
9. Estimated creatinine clearance \< 30 mL/min
10. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5 times the upper limit of normal.
11. Hemoglobin \< 75% of the lower limit of the normal range.
12. Systolic blood pressure \< 100 mmHg.
13. Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements.
14. Pregnant or breast-feeding.
15. Known concomitant life-threatening disease with a life expectancy \< 12 months.
16. Body weight \< 40 kg.
17. Any condition that prevents compliance with the protocol or adherence to therapy.
18. Recently started (\< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise.
19. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization.
20. Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors).
21. Treatment with cytochrome P3A (CYP3A) inducers within 4 weeks prior to randomization
22. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
23. Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.

Primary outcomes:
measure: Time to First Confirmed Morbidity or Mortality Event up to the End of Treatment (Kaplan-Meier Estimate of Patients Without a Morbidity or Mortality Event)
timeFrame: Up to end of treatment (data presented up to month 36)
Secondary outcomes:
measure: Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
timeFrame: Up to end of treatment (data presented up to month 36)
measure: Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
timeFrame: Up to end of treatment (data presented up to month 36)
measure: Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event)
timeFrame: Up to end of study (data presented up to month 36)
measure: Change From Baseline to Month 6 in 6-minute Walk Distance
timeFrame: Baseline to month 6
measure: Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6
timeFrame: Baseline to month 6
measure: Pulmonary Vascular Resistance at Baseline and Month 6
timeFrame: Baseline to month 6
measure: Cardiac Index at Baseline and Month 6
timeFrame: Baseline to month 6
Other outcomes:
measure: Summary of the First Causes of Morbidity or Mortality
timeFrame: Up to end of treatment (Up to 36 months)
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Pheonix
country: United States
facility: Arizona Pulmonary Specialists
state: Arizona
city: Los Angeles
country: United States
facility: GLVA Healthcare Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Cottage Hospital
state: California
city: Torrance
country: United States
facility: Liu Center for Pulmonary Hypertension
state: California
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
state: Georgia
city: Atlanta
country: United States
facility: Pulmonary & Critical Care of Atlanta
state: Georgia
city: Decatur
country: United States
facility: Southeastern Lung Care
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associate, PLLC
state: Kentucky
city: New Orleans
country: United States
facility: Medical Center of Louisiana at New Orleans
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: Boston
country: United States
facility: Pulmonary/Critical Care Division/Tufts New England Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: University of NJ - Robert Wood Johnson Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center - Pediatric Cardiology
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Ohio Heart Health Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Medical Center - St. Paul University
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine and the Methodist Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Dept. of Pulmonary Medicine - Latter Day Saints Hospital
state: Utah
city: Norfolk
country: United States
facility: Sentara Hospital T/A Sentara Cardiovascular Research Institute
state: Virginia
city: Milwaukee
country: United States
facility: Comprehensive Cardiovascular Care Group
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Fundacion Favaloro
city: Buenos Aires
country: Argentina
facility: Hospital Britanico
city: Buenos Aires
country: Argentina
facility: Sanatorio MITRE
city: Buenos Aires
country: Argentina
facility: SANATORIO OTAMENDI y MIROLI
city: Cordoba
country: Argentina
facility: Htal Italiano Cordoba
city: Cordoba
country: Argentina
facility: Htla privado de Cordoba
city: Corrientes
country: Argentina
facility: Instituto Cardiologia Corrientes
city: Santa Fe
country: Argentina
facility: 'Hospital Italiano - Garibaldi de Rosario
city: Darlinghurst, NSW
country: Australia
facility: St. Vincent's Hospital
city: Melbourne, VIC
country: Australia
facility: The Alfred Hospital
city: Sunshine Coast
country: Australia
facility: Royal Brisbane Hospital
city: Vienna
country: Austria
facility: Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
city: Minsk
country: Belarus
facility: Republican reserach - Pratical Centre of Cardilogy
city: Minsk
country: Belarus
facility: Minsk Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Hospital
city: Leuven
country: Belgium
facility: University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology
city: London
country: Canada
facility: London Health Sciences Centre / Victoria Hospital
state: Ontario
city: Saint-Foy
country: Canada
facility: L'Hopital Laval
state: Quebec
city: Calgary
country: Canada
facility: Peter Lougheed Centre
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Vancouver
country: Canada
facility: Vancouver General Hospital
city: Santiago de Chile
country: Chile
facility: 'Pontificia Universidad Catolica de Chile
city: Santiago de Chile
country: Chile
facility: Hospital del Torax
city: Santiago
country: Chile
facility: Hospital San Juan de Dios
city: Guangzhou
country: China
facility: Guangdong General Hospital, Cardiology Department
state: Guangdong
city: Nanjing
country: China
facility: Jiangsu Province Hospital - Pneumology Department
state: Jiangsu
city: Beijing
country: China
facility: Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
city: Beijing
country: China
facility: Peking Union Medcical College Hospital, Rheumatology Department
city: Beijing
country: China
facility: Chinese PLA General Hospital (301 Hospital), Cardiology Department
city: Shanghai
country: China
facility: Renji Hospital, Rheumatology Dept
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University, Cardiology Dept
city: Shanghai
country: China
facility: Renji Hospital, Cardiology Dept
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
city: Bogota
country: Colombia
facility: Fundación Clínica Shaio
city: Floridablanca, Santander
country: Colombia
facility: 'Fundacion Cardiovascular de Colombia
city: Rijeka
country: Croatia
facility: Clinical Hospital Center
city: Clamart
country: France
facility: Hôpital Antoine Béclère / Service de Pneumologie
city: Montpellier Cedex 5
country: France
facility: Hôpital Arnaud de Villeneuve Service des Maladies Respiratoires
city: Pessac
country: France
facility: Hopital Haut-Leveque - Maison du Haut-Leveque
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin, Klinik für Innere Medizin
city: Dresden
country: Germany
facility: Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
city: Giessen
country: Germany
facility: Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med.
city: Greifswald
country: Germany
facility: Universität Greifswald / Klinik für Innere Medizin B,
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
city: Homburg/Saar
country: Germany
facility: Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
city: Koln
country: Germany
facility: Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
city: Leipzig
country: Germany
facility: Universtätsklinik Leipzig
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik
city: Munich
country: Germany
facility: Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg / Innere Medizin II
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital / Division of Cardiology, Department of Medicine
city: Budapest
country: Hungary
facility: Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
city: Budapest
country: Hungary
facility: Semmelweis University, Pulmonolgy Clinic
city: Szeged
country: Hungary
facility: University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center
city: Ahmedabad
country: India
facility: Life Care Institute of Medical Science & Research, Ahmedabad
city: Delhi
country: India
facility: G B Pant Hospital & Maulana Azad Medical College
city: Hyderabad
country: India
facility: Care Hospital
city: Mumbai
country: India
facility: King Edward VII Memorial Hospital (KEM) Hospital
city: Mumbai
country: India
facility: P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital and Research Centre
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
city: Petach - Tikvah
country: Israel
facility: Rabin Medical Center - Belinson campus - Pulmonary Institute
city: Rehovot
country: Israel
facility: Pulmonary Institute, Kaplan Medical Center
city: Tel Hashomer
country: Israel
facility: The pulmonary institute Sheba Medical centre
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
city: Roma
country: Italy
facility: Policlinico Umberto I, Cardiologia
city: Kuala Lumpur
country: Malaysia
facility: Institut Jantung Negara (National Heart Institute)
city: Mexico City
country: Mexico
facility: 'Instituto Nacional de Cardiología (INC) Ignacio Chávez
city: Monterrey Nuevo León
country: Mexico
facility: Unidad de Investigación Clinica en Medicina, SC
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis
city: Oslo
country: Norway
facility: Aker University Dept of Cardilogy
city: Lima
country: Peru
facility: Hospital Alberto Sabogal Sologuren - EsSALUD
city: Lima
country: Peru
facility: IInstituto de Enfermedades Respiratorias, Clinica San Gabriel
city: Krakow
country: Poland
facility: Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
city: Warszawa
country: Poland
facility: Klinika Chorób Wewnętrznych Klatki Piersiowej
city: Zabrze
country: Poland
facility: III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
city: Bucharest
country: Romania
facility: Institutul de boli cardiovasculare / Clinica de Cardiologie
city: Bucharest
country: Romania
facility: Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
city: Ekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
city: Kemerovo
country: Russian Federation
facility: Municipal Health Care Institution "Kemerovo Cardiology Dispensary"
city: Moscow
country: Russian Federation
facility: Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
city: Moscow
country: Russian Federation
facility: State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
city: Moscow
country: Russian Federation
facility: Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
city: St. Petersburg
country: Russian Federation
facility: Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
city: St. Petersburg
country: Russian Federation
facility: State Educational Institution of High Professional Education
city: Tomsk
country: Russian Federation
facility: State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
city: Tomsk
country: Russian Federation
facility: Tomsk Regional Clinical Hospital / Pulmonology Unit
city: Yaroslavl
country: Russian Federation
facility: Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
city: Belgrade
country: Serbia
facility: University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA)
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis
city: Belgrade
country: Serbia
facility: Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology
city: Singapore
country: Singapore
facility: National University Hospital/ The Heart Institute
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Bratislava
country: Slovakia
facility: National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation
city: Bratislava
country: Slovakia
facility: Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology
city: Johannesburg
country: South Africa
facility: Netcare Milpark Hospital,Center for Chest Disease
city: Johannesburg
country: South Africa
facility: Chris Hani Baragwanath Hospital, Department of Cardiology
city: Parow
country: South Africa
facility: Tread Research
city: Somerset West
country: South Africa
facility: Block 4, Vergelegen Medi-Clinic
city: A Coruna
country: Spain
facility: Hospital Juan Canalejo Servicio de Neumología
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General
city: Barcelona
country: Spain
facility: Hospital Clínico I Provincial, Servicio de Neumología.
city: Madrid
country: Spain
facility: Hospital 12 Octubre/ Cardiology department Planta 5a.
city: Malaga
country: Spain
facility: Hospital Clínico Virgen de la Victoria / Pneumology Unit,
city: Pontevedra
country: Spain
facility: Hospital Montecelo, Servicio de Neumología
city: Lund
country: Sweden
facility: University Hospital in Lund, Heart and Lung Division
city: Uppsala
country: Sweden
facility: Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
city: Bangkok
country: Thailand
facility: Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
city: Chiang Mai
country: Thailand
facility: Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
city: Istanbul
country: Turkey
facility: Istanbul University Cardiology Institure
city: Dnepropetrovsk
country: Ukraine
facility: Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
city: Lviv
country: Ukraine
facility: Danylo Halytskyi Lviv State Medical University
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Actelion
name: Loic Perchenet, PhD
role: STUDY_CHAIR
References:
citation: Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Jing ZC, Le Brun FO, Mehta S, Mittelholzer CM, Perchenet L, Sastry BK, Sitbon O, Souza R, Torbicki A, Zeng X, Rubin LJ, Simonneau G; SERAPHIN Investigators. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013 Aug 29;369(9):809-18. doi: 10.1056/NEJMoa1213917.
citation: Di Scala L, Bacchi M, Bayer B, Turricchia S. Adjusting Overall Survival Estimates of Macitentan in Pulmonary Arterial Hypertension After Treatment Switching: Results from the SERAPHIN Study. Adv Ther. 2022 Sep;39(9):4346-4358. doi: 10.1007/s12325-022-02253-8. Epub 2022 Aug 1.
citation: Souza R, Delcroix M, Galie N, Jansa P, Mehta S, Pulido T, Rubin L, Sastry BKS, Simonneau G, Sitbon O, Torbicki A, Boyanova N, Chamitava L, Stein C, Channick RN. Long-Term Safety, Tolerability and Survival in Patients with Pulmonary Arterial Hypertension Treated with Macitentan: Results from the SERAPHIN Open-Label Extension. Adv Ther. 2022 Sep;39(9):4374-4390. doi: 10.1007/s12325-022-02199-x. Epub 2022 Jul 12.
citation: Torbicki A, Bacchi M, Delcroix M, Farber HW, Ghofrani HA, Hennessy B, Jansa P, Mehta S, Perchenet L, Pulido T, Rosenberg D, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Wei LJ, Channick R, Benza R. Integrating Data From Randomized Controlled Trials and Observational Studies to Assess Survival in Rare Diseases. Circ Cardiovasc Qual Outcomes. 2019 May;12(5):e005095. doi: 10.1161/CIRCOUTCOMES.118.005095.
citation: Krause A, Zisowsky J, Dingemanse J. Modeling of pharmacokinetics, efficacy, and hemodynamic effects of macitentan in patients with pulmonary arterial hypertension. Pulm Pharmacol Ther. 2018 Apr;49:140-146. doi: 10.1016/j.pupt.2018.02.005. Epub 2018 Feb 28.
citation: McLaughlin VV, Hoeper MM, Channick RN, Chin KM, Delcroix M, Gaine S, Ghofrani HA, Jansa P, Lang IM, Mehta S, Pulido T, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Tapson VF, Perchenet L, Preiss R, Verweij P, Rubin LJ, Galie N. Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality. J Am Coll Cardiol. 2018 Feb 20;71(7):752-763. doi: 10.1016/j.jacc.2017.12.010.
citation: Jansa P, Pulido T. Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Trial. Am J Cardiovasc Drugs. 2018 Feb;18(1):1-11. doi: 10.1007/s40256-017-0260-1.
citation: Mehta S, Sastry BKS, Souza R, Torbicki A, Ghofrani HA, Channick RN, Delcroix M, Pulido T, Simonneau G, Wlodarczyk J, Rubin LJ, Jansa P, Hunsche E, Galie N, Perchenet L, Sitbon O. Macitentan Improves Health-Related Quality of Life for Patients With Pulmonary Arterial Hypertension: Results From the Randomized Controlled SERAPHIN Trial. Chest. 2017 Jan;151(1):106-118. doi: 10.1016/j.chest.2016.08.1473. Epub 2016 Sep 23.
citation: Simonneau G, Channick RN, Delcroix M, Galie N, Ghofrani HA, Jansa P, Le Brun FO, Mehta S, Perchenet L, Pulido T, Sastry BK, Sitbon O, Souza R, Torbicki A, Rubin LJ. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015 Dec;46(6):1711-20. doi: 10.1183/13993003.00364-2015. Epub 2015 Oct 22.
citation: Channick RN, Delcroix M, Ghofrani HA, Hunsche E, Jansa P, Le Brun FO, Mehta S, Pulido T, Rubin LJ, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Galie N. Effect of macitentan on hospitalizations: results from the SERAPHIN trial. JACC Heart Fail. 2015 Jan;3(1):1-8. doi: 10.1016/j.jchf.2014.07.013. Epub 2014 Nov 11.