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Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension (SERAPHIN)

Primary Purpose

Pulmonary Arterial Hypertension

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
macitentan (ACT-064992)
macitentan (ACT-064992)
placebo
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring pulmonary arterial hypertension SERAPHIN

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama at Birmingham
  • Arizona Pulmonary Specialists
  • GLVA Healthcare Center
  • University of California, San Diego
  • Santa Barbara Cottage Hospital
  • Liu Center for Pulmonary Hypertension
  • University of Colorado Health Sciences Center
  • Mayo Clinic, Jacksonville
  • Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
  • Pulmonary & Critical Care of Atlanta
  • Southeastern Lung Care
  • University of Chicago Hospitals
  • University of Iowa
  • University of Kansas Medical Center
  • Kentuckiana Pulmonary Associate, PLLC
  • Medical Center of Louisiana at New Orleans
  • Maine Medical Center
  • University of Maryland School of Medicine
  • Boston University School of Medicine
  • Pulmonary/Critical Care Division/Tufts New England Medical Center
  • University of Michigan
  • Washington University School of Medicine
  • University of NJ - Robert Wood Johnson Medical School
  • Columbia University Medical Center - Pediatric Cardiology
  • Duke University Medical Center
  • University of Cincinnati Ohio Heart Health Center
  • Ohio State University
  • Vanderbilt University Medical Center
  • University of Texas Medical Center - St. Paul University
  • Baylor College of Medicine and the Methodist Hospital
  • Dept. of Pulmonary Medicine - Latter Day Saints Hospital
  • Sentara Hospital T/A Sentara Cardiovascular Research Institute
  • Comprehensive Cardiovascular Care Group
  • Fundacion Favaloro
  • Hospital Britanico
  • Sanatorio MITRE
  • SANATORIO OTAMENDI y MIROLI
  • Htal Italiano Cordoba
  • Htla privado de Cordoba
  • Instituto Cardiologia Corrientes
  • 'Hospital Italiano - Garibaldi de Rosario
  • St. Vincent's Hospital
  • The Alfred Hospital
  • Royal Brisbane Hospital
  • Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
  • Republican reserach - Pratical Centre of Cardilogy
  • Minsk Regional Clinical Hospital
  • Vitebsk Regional Clinical Hospital
  • University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie
  • Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology
  • London Health Sciences Centre / Victoria Hospital
  • L'Hopital Laval
  • Peter Lougheed Centre
  • Toronto General Hospital
  • Vancouver General Hospital
  • 'Pontificia Universidad Catolica de Chile
  • Hospital del Torax
  • Hospital San Juan de Dios
  • Guangdong General Hospital, Cardiology Department
  • Jiangsu Province Hospital - Pneumology Department
  • Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
  • Peking Union Medcical College Hospital, Rheumatology Department
  • Chinese PLA General Hospital (301 Hospital), Cardiology Department
  • Renji Hospital, Rheumatology Dept
  • Zhongshan Hospital Fudan University, Cardiology Dept
  • Renji Hospital, Cardiology Dept
  • Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
  • Fundación Clínica Shaio
  • 'Fundacion Cardiovascular de Colombia
  • Clinical Hospital Center
  • Hôpital Antoine Béclère / Service de Pneumologie
  • Hôpital Arnaud de Villeneuve Service des Maladies Respiratoires
  • Hopital Haut-Leveque - Maison du Haut-Leveque
  • Unfallkrankenhaus Berlin, Klinik für Innere Medizin
  • Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
  • Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med.
  • Universität Greifswald / Klinik für Innere Medizin B,
  • Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
  • Thoraxklinik am Universitätsklinikum Heidelberg
  • Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
  • Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
  • Universtätsklinik Leipzig
  • Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik
  • Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
  • Universitätsklinikum Regensburg / Innere Medizin II
  • Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
  • Queen Mary Hospital / Division of Cardiology, Department of Medicine
  • Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
  • Semmelweis University, Pulmonolgy Clinic
  • University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center
  • Life Care Institute of Medical Science & Research, Ahmedabad
  • G B Pant Hospital & Maulana Azad Medical College
  • Care Hospital
  • King Edward VII Memorial Hospital (KEM) Hospital
  • P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
  • Deenanath Mangeshkar Hospital and Research Centre
  • Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
  • Rabin Medical Center - Belinson campus - Pulmonary Institute
  • Pulmonary Institute, Kaplan Medical Center
  • The pulmonary institute Sheba Medical centre
  • Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
  • Policlinico Umberto I, Cardiologia
  • Institut Jantung Negara (National Heart Institute)
  • 'Instituto Nacional de Cardiología (INC) Ignacio Chávez
  • Unidad de Investigación Clinica en Medicina, SC
  • St. Antonius ziekenhuis
  • Aker University Dept of Cardilogy
  • Hospital Alberto Sabogal Sologuren - EsSALUD
  • IInstituto de Enfermedades Respiratorias, Clinica San Gabriel
  • Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
  • Klinika Chorób Wewnętrznych Klatki Piersiowej
  • III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
  • Institutul de boli cardiovasculare / Clinica de Cardiologie
  • Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
  • Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
  • Municipal Health Care Institution "Kemerovo Cardiology Dispensary"
  • Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
  • State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
  • Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
  • Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
  • State Educational Institution of High Professional Education
  • State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
  • Tomsk Regional Clinical Hospital / Pulmonology Unit
  • Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
  • University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA)
  • University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis
  • Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology
  • National University Hospital/ The Heart Institute
  • Singapore General Hospital
  • National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation
  • Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology
  • Netcare Milpark Hospital,Center for Chest Disease
  • Chris Hani Baragwanath Hospital, Department of Cardiology
  • Tread Research
  • Block 4, Vergelegen Medi-Clinic
  • Hospital Juan Canalejo Servicio de Neumología
  • Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General
  • Hospital Clínico I Provincial, Servicio de Neumología.
  • Hospital 12 Octubre/ Cardiology department Planta 5a.
  • Hospital Clínico Virgen de la Victoria / Pneumology Unit,
  • Hospital Montecelo, Servicio de Neumología
  • University Hospital in Lund, Heart and Lung Division
  • Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar
  • Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology
  • National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
  • Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
  • Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
  • Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University
  • Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
  • Istanbul University Cardiology Institure
  • Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
  • Danylo Halytskyi Lviv State Medical University
  • Royal Free Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

Arm Description

Macitentan (ACT-064992) tablet, 3 mg, once daily

Macitentan (ACT-064992) tablet, 10 mg, once daily

Matching placebo, once daily

Outcomes

Primary Outcome Measures

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)
Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics

Secondary Outcome Measures

Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Events of PAH or hospitalization for PAH up to the end of treatment included: death due to PAH, or onset of a treatment-emergent adverse event with a fatal outcome due to PAH occurring up to 4 weeks after the end of treatment, or hospitalisation for PAH up to the end of treatment.
Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Events of death due to any cause up to the end of treatment (plus 7 days)
Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event)
Events of death due to any cause up to the end of study (EOS). The initiation of EOS procedure occurred when the target of 285 events was expected to have been achieved (30 January 2012).
Change From Baseline to Month 6 in 6-minute Walk Distance
The 6-minute walk test (6MWT) is a non-encouraged test, performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. These guidelines were provided to all sites. For patients who had never performed a 6MWT previously, a training test was required before the qualifying tests for inclusion were performed.
Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6
Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA.
Pulmonary Vascular Resistance at Baseline and Month 6
In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period.
Cardiac Index at Baseline and Month 6
In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period.

Full Information

First Posted
April 14, 2008
Last Updated
September 10, 2015
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT00660179
Brief Title
Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension
Acronym
SERAPHIN
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

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
March 2012 (Actual)
Study Completion Date
April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
pulmonary arterial hypertension SERAPHIN

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
742 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Macitentan (ACT-064992) tablet, 3 mg, once daily
Arm Title
2
Arm Type
Experimental
Arm Description
Macitentan (ACT-064992) tablet, 10 mg, once daily
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
Matching placebo, once daily
Intervention Type
Drug
Intervention Name(s)
macitentan (ACT-064992)
Intervention Description
Tablet, 3 mg dosage, once daily
Intervention Type
Drug
Intervention Name(s)
macitentan (ACT-064992)
Intervention Description
Tablet, 10 mg dosage, once daily
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Matching placebo, once daily
Primary Outcome Measure Information:
Title
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)
Description
Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics
Time Frame
Up to end of treatment (data presented up to month 36)
Secondary Outcome Measure Information:
Title
Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Description
Events of PAH or hospitalization for PAH up to the end of treatment included: death due to PAH, or onset of a treatment-emergent adverse event with a fatal outcome due to PAH occurring up to 4 weeks after the end of treatment, or hospitalisation for PAH up to the end of treatment.
Time Frame
Up to end of treatment (data presented up to month 36)
Title
Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Description
Events of death due to any cause up to the end of treatment (plus 7 days)
Time Frame
Up to end of treatment (data presented up to month 36)
Title
Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event)
Description
Events of death due to any cause up to the end of study (EOS). The initiation of EOS procedure occurred when the target of 285 events was expected to have been achieved (30 January 2012).
Time Frame
Up to end of study (data presented up to month 36)
Title
Change From Baseline to Month 6 in 6-minute Walk Distance
Description
The 6-minute walk test (6MWT) is a non-encouraged test, performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. These guidelines were provided to all sites. For patients who had never performed a 6MWT previously, a training test was required before the qualifying tests for inclusion were performed.
Time Frame
Baseline to month 6
Title
Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6
Description
Class I: no limitation of usual physical activity (PA) which does not increase dyspnea, fatigue, chest pain, or presyncope. Class II: mild limitation of PA. No discomfort at rest. Normal PA increases dyspnea, fatigue, chest pain, or presyncope. Class III: marked limitation of PA. No discomfort at rest. Less than ordinary activity increases dyspnea, fatigue, chest pain, or presyncope. Class IV: unable to perform any PA and who may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest and symptoms are increased by almost any PA.
Time Frame
Baseline to month 6
Title
Pulmonary Vascular Resistance at Baseline and Month 6
Description
In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period.
Time Frame
Baseline to month 6
Title
Cardiac Index at Baseline and Month 6
Description
In a sub-study, hemodynamic variables were assessed at baseline and Month 6. If the patient had undergone a right heart catheterization during the 3 months prior to randomization, these results were to be used as baseline values, if the background therapy had not changed during the intervening period.
Time Frame
Baseline to month 6
Other Pre-specified Outcome Measures:
Title
Summary of the First Causes of Morbidity or Mortality
Description
Morbidity or mortality events were defined as: a) Death; b) Atrial septostomy; c) Lung transplantation; d) Initiation of intravenous (i.v.) or subcutaneous prostanoids, or; e) Other worsening of pulmonary arterial hypertension (PAH). Other worsening of PAH was defined by the combined occurrence of all the following 3 events: At least 15% decrease in the 6 minute walk distance from baseline, confirmed by 2 tests performed on separate days, within 2 weeks. AND worsening of PAH symptoms including at least one of the following: a) Increase in WHO Functional Class (WHO FC), or no change in patients in WHO FC IV at baseline; b) Appearance or worsening of signs of right heart failure that did not respond to optimized oral diuretic therapy AND need for new treatment(s) for PAH that included the following: a) Oral or inhaled prostanoids; b) Oral phosphodiesterase inhibitors; c) Endothelin receptor antagonists (only after discontinuation of study treatment; d) i.v. diuretics
Time Frame
Up to end of treatment (Up to 36 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent prior to initiation of any study mandated procedure. Patients with symptomatic pulmonary arterial hypertension (PAH) in modified World Health Organization (WHO) functional class II to IV. 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. 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. 6-minute walk distance (6MWD) >= 50 m. 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: PAH associated with portal hypertension, thyroid disorders, glycogen storage disease, Gaucher''s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders or splenectomy. PAH associated with non corrected simple congenital systemic-to-pulmonary shunts, and combined and complex systemic-to-pulmonary shunts, corrected or non corrected. PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg), known pulmonary veno-occlusive disease, and pulmonary capillary hemangiomatosis. Persistent pulmonary hypertension of the newborn. Pulmonary Hypertension belonging to groups 2 to 5 of the Venice classification. 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. Moderate to severe restrictive lung disease: total lung capacity (TLC) < 60% of predicted value. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C. Estimated creatinine clearance < 30 mL/min Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal. Hemoglobin < 75% of the lower limit of the normal range. Systolic blood pressure < 100 mmHg. Acute or chronic physical impairment (other than dyspnea), limiting the ability to comply with study requirements. Pregnant or breast-feeding. Known concomitant life-threatening disease with a life expectancy < 12 months. Body weight < 40 kg. Any condition that prevents compliance with the protocol or adherence to therapy. Recently started (< 8 weeks prior to randomization) or planned cardio-pulmonary rehabilitation program based on exercise. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to randomization. Systemic treatment within 4 week prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors). Treatment with cytochrome P3A (CYP3A) inducers within 4 weeks prior to randomization Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients. Planned treatment, or treatment, with another investigational drug within 1 month prior to randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loic Perchenet, PhD
Organizational Affiliation
Actelion
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249-0001
Country
United States
Facility Name
Arizona Pulmonary Specialists
City
Pheonix
State/Province
Arizona
ZIP/Postal Code
85013
Country
United States
Facility Name
GLVA Healthcare Center
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
Santa Barbara Cottage Hospital
City
Santa Barbara
State/Province
California
Country
United States
Facility Name
Liu Center for Pulmonary Hypertension
City
Torrance
State/Province
California
Country
United States
Facility Name
University of Colorado Health Sciences Center
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Mayo Clinic, Jacksonville
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Pulmonary & Critical Care of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Southeastern Lung Care
City
Decatur
State/Province
Georgia
Country
United States
Facility Name
University of Chicago Hospitals
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kentuckiana Pulmonary Associate, PLLC
City
Louisville
State/Province
Kentucky
Country
United States
Facility Name
Medical Center of Louisiana at New Orleans
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Maine Medical Center
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
University of Maryland School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Pulmonary/Critical Care Division/Tufts New England Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of NJ - Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
Country
United States
Facility Name
Columbia University Medical Center - Pediatric Cardiology
City
New York
State/Province
New York
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
University of Cincinnati Ohio Heart Health Center
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
University of Texas Medical Center - St. Paul University
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Baylor College of Medicine and the Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Dept. of Pulmonary Medicine - Latter Day Saints Hospital
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
Sentara Hospital T/A Sentara Cardiovascular Research Institute
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Comprehensive Cardiovascular Care Group
City
Milwaukee
State/Province
Wisconsin
Country
United States
Facility Name
Fundacion Favaloro
City
Buenos Aires
ZIP/Postal Code
C1093AAS
Country
Argentina
Facility Name
Hospital Britanico
City
Buenos Aires
Country
Argentina
Facility Name
Sanatorio MITRE
City
Buenos Aires
Country
Argentina
Facility Name
SANATORIO OTAMENDI y MIROLI
City
Buenos Aires
Country
Argentina
Facility Name
Htal Italiano Cordoba
City
Cordoba
Country
Argentina
Facility Name
Htla privado de Cordoba
City
Cordoba
Country
Argentina
Facility Name
Instituto Cardiologia Corrientes
City
Corrientes
Country
Argentina
Facility Name
'Hospital Italiano - Garibaldi de Rosario
City
Santa Fe
Country
Argentina
Facility Name
St. Vincent's Hospital
City
Darlinghurst, NSW
ZIP/Postal Code
2010
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne, VIC
ZIP/Postal Code
3181
Country
Australia
Facility Name
Royal Brisbane Hospital
City
Sunshine Coast
ZIP/Postal Code
4558
Country
Australia
Facility Name
Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
City
Vienna
Country
Austria
Facility Name
Republican reserach - Pratical Centre of Cardilogy
City
Minsk
ZIP/Postal Code
220036
Country
Belarus
Facility Name
Minsk Regional Clinical Hospital
City
Minsk
ZIP/Postal Code
223040
Country
Belarus
Facility Name
Vitebsk Regional Clinical Hospital
City
Vitebsk
ZIP/Postal Code
210037
Country
Belarus
Facility Name
University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie
City
Leuven
Country
Belgium
Facility Name
Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
London Health Sciences Centre / Victoria Hospital
City
London
State/Province
Ontario
Country
Canada
Facility Name
L'Hopital Laval
City
Saint-Foy
State/Province
Quebec
Country
Canada
Facility Name
Peter Lougheed Centre
City
Calgary
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
Country
Canada
Facility Name
Vancouver General Hospital
City
Vancouver
ZIP/Postal Code
V6Z 1Y6
Country
Canada
Facility Name
'Pontificia Universidad Catolica de Chile
City
Santiago de Chile
Country
Chile
Facility Name
Hospital del Torax
City
Santiago de Chile
Country
Chile
Facility Name
Hospital San Juan de Dios
City
Santiago
Country
Chile
Facility Name
Guangdong General Hospital, Cardiology Department
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Facility Name
Jiangsu Province Hospital - Pneumology Department
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Facility Name
Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
City
Beijing
ZIP/Postal Code
100029
Country
China
Facility Name
Peking Union Medcical College Hospital, Rheumatology Department
City
Beijing
ZIP/Postal Code
100032
Country
China
Facility Name
Chinese PLA General Hospital (301 Hospital), Cardiology Department
City
Beijing
ZIP/Postal Code
100853
Country
China
Facility Name
Renji Hospital, Rheumatology Dept
City
Shanghai
ZIP/Postal Code
200001
Country
China
Facility Name
Zhongshan Hospital Fudan University, Cardiology Dept
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Renji Hospital, Cardiology Dept
City
Shanghai
ZIP/Postal Code
200127
Country
China
Facility Name
Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
Fundación Clínica Shaio
City
Bogota
Country
Colombia
Facility Name
'Fundacion Cardiovascular de Colombia
City
Floridablanca, Santander
Country
Colombia
Facility Name
Clinical Hospital Center
City
Rijeka
ZIP/Postal Code
51 000
Country
Croatia
Facility Name
Hôpital Antoine Béclère / Service de Pneumologie
City
Clamart
ZIP/Postal Code
92140
Country
France
Facility Name
Hôpital Arnaud de Villeneuve Service des Maladies Respiratoires
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Haut-Leveque - Maison du Haut-Leveque
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Unfallkrankenhaus Berlin, Klinik für Innere Medizin
City
Berlin
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med.
City
Giessen
ZIP/Postal Code
D-35392
Country
Germany
Facility Name
Universität Greifswald / Klinik für Innere Medizin B,
City
Greifswald
ZIP/Postal Code
D-17487
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
Thoraxklinik am Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
D-69126
Country
Germany
Facility Name
Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
City
Homburg/Saar
ZIP/Postal Code
D-66421
Country
Germany
Facility Name
Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
City
Koln
ZIP/Postal Code
D-50924
Country
Germany
Facility Name
Universtätsklinik Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik
City
Mainz
ZIP/Postal Code
D-55131
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
City
Munich
ZIP/Postal Code
D-81377
Country
Germany
Facility Name
Universitätsklinikum Regensburg / Innere Medizin II
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
City
Hong Kong
Country
Hong Kong
Facility Name
Queen Mary Hospital / Division of Cardiology, Department of Medicine
City
Hong Kong
Country
Hong Kong
Facility Name
Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
City
Budapest
ZIP/Postal Code
H-1096
Country
Hungary
Facility Name
Semmelweis University, Pulmonolgy Clinic
City
Budapest
ZIP/Postal Code
H-1125
Country
Hungary
Facility Name
University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center
City
Szeged
Country
Hungary
Facility Name
Life Care Institute of Medical Science & Research, Ahmedabad
City
Ahmedabad
ZIP/Postal Code
382428
Country
India
Facility Name
G B Pant Hospital & Maulana Azad Medical College
City
Delhi
ZIP/Postal Code
110049
Country
India
Facility Name
Care Hospital
City
Hyderabad
ZIP/Postal Code
500001
Country
India
Facility Name
King Edward VII Memorial Hospital (KEM) Hospital
City
Mumbai
ZIP/Postal Code
400 012
Country
India
Facility Name
P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
City
Mumbai
ZIP/Postal Code
400016
Country
India
Facility Name
Deenanath Mangeshkar Hospital and Research Centre
City
Pune
ZIP/Postal Code
411 004
Country
India
Facility Name
Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Rabin Medical Center - Belinson campus - Pulmonary Institute
City
Petach - Tikvah
ZIP/Postal Code
49100
Country
Israel
Facility Name
Pulmonary Institute, Kaplan Medical Center
City
Rehovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
The pulmonary institute Sheba Medical centre
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
City
Tel-Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Policlinico Umberto I, Cardiologia
City
Roma
ZIP/Postal Code
00161
Country
Italy
Facility Name
Institut Jantung Negara (National Heart Institute)
City
Kuala Lumpur
ZIP/Postal Code
50400
Country
Malaysia
Facility Name
'Instituto Nacional de Cardiología (INC) Ignacio Chávez
City
Mexico City
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Unidad de Investigación Clinica en Medicina, SC
City
Monterrey Nuevo León
ZIP/Postal Code
64020
Country
Mexico
Facility Name
St. Antonius ziekenhuis
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
Facility Name
Aker University Dept of Cardilogy
City
Oslo
ZIP/Postal Code
N0514
Country
Norway
Facility Name
Hospital Alberto Sabogal Sologuren - EsSALUD
City
Lima
Country
Peru
Facility Name
IInstituto de Enfermedades Respiratorias, Clinica San Gabriel
City
Lima
Country
Peru
Facility Name
Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Klinika Chorób Wewnętrznych Klatki Piersiowej
City
Warszawa
ZIP/Postal Code
01-138
Country
Poland
Facility Name
III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
City
Zabrze
ZIP/Postal Code
41-800
Country
Poland
Facility Name
Institutul de boli cardiovasculare / Clinica de Cardiologie
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
City
Bucharest
ZIP/Postal Code
50159
Country
Romania
Facility Name
Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
City
Ekaterinburg
ZIP/Postal Code
620102
Country
Russian Federation
Facility Name
Municipal Health Care Institution "Kemerovo Cardiology Dispensary"
City
Kemerovo
ZIP/Postal Code
650002
Country
Russian Federation
Facility Name
Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
City
Moscow
ZIP/Postal Code
105077
Country
Russian Federation
Facility Name
State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
City
Moscow
ZIP/Postal Code
117049
Country
Russian Federation
Facility Name
Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
City
Moscow
ZIP/Postal Code
121552
Country
Russian Federation
Facility Name
Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
City
St. Petersburg
ZIP/Postal Code
194156
Country
Russian Federation
Facility Name
State Educational Institution of High Professional Education
City
St. Petersburg
ZIP/Postal Code
197 022
Country
Russian Federation
Facility Name
State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
City
Tomsk
ZIP/Postal Code
634063
Country
Russian Federation
Facility Name
Tomsk Regional Clinical Hospital / Pulmonology Unit
City
Tomsk
ZIP/Postal Code
634063
Country
Russian Federation
Facility Name
Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
City
Yaroslavl
ZIP/Postal Code
150 003
Country
Russian Federation
Facility Name
University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA)
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology
City
Belgrade
ZIP/Postal Code
11080
Country
Serbia
Facility Name
National University Hospital/ The Heart Institute
City
Singapore
ZIP/Postal Code
168752
Country
Singapore
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
168752
Country
Singapore
Facility Name
National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation
City
Bratislava
ZIP/Postal Code
833 48
Country
Slovakia
Facility Name
Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology
City
Bratislava
ZIP/Postal Code
833 48
Country
Slovakia
Facility Name
Netcare Milpark Hospital,Center for Chest Disease
City
Johannesburg
ZIP/Postal Code
2000
Country
South Africa
Facility Name
Chris Hani Baragwanath Hospital, Department of Cardiology
City
Johannesburg
ZIP/Postal Code
27-11-033 8197
Country
South Africa
Facility Name
Tread Research
City
Parow
ZIP/Postal Code
7505
Country
South Africa
Facility Name
Block 4, Vergelegen Medi-Clinic
City
Somerset West
ZIP/Postal Code
7130
Country
South Africa
Facility Name
Hospital Juan Canalejo Servicio de Neumología
City
A Coruna
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clínico I Provincial, Servicio de Neumología.
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital 12 Octubre/ Cardiology department Planta 5a.
City
Madrid
ZIP/Postal Code
20841
Country
Spain
Facility Name
Hospital Clínico Virgen de la Victoria / Pneumology Unit,
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Montecelo, Servicio de Neumología
City
Pontevedra
ZIP/Postal Code
36771
Country
Spain
Facility Name
University Hospital in Lund, Heart and Lung Division
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
City
Taipei
Country
Taiwan
Facility Name
Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University
City
Chiang Mai
Country
Thailand
Facility Name
Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand
Facility Name
Istanbul University Cardiology Institure
City
Istanbul
Country
Turkey
Facility Name
Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
City
Dnepropetrovsk
ZIP/Postal Code
49060
Country
Ukraine
Facility Name
Danylo Halytskyi Lviv State Medical University
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23984728
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.
Results Reference
result
PubMed Identifier
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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.
Results Reference
derived
PubMed Identifier
35819570
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.
Results Reference
derived
PubMed Identifier
31109190
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.
Results Reference
derived
PubMed Identifier
29501590
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.
Results Reference
derived
PubMed Identifier
29447737
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.
Results Reference
derived
PubMed Identifier
29280064
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.
Results Reference
derived
PubMed Identifier
27671974
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. Erratum In: Chest. 2018 May;153(5):1287.
Results Reference
derived
PubMed Identifier
26493786
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.
Results Reference
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PubMed Identifier
25457902
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.
Results Reference
derived

Learn more about this trial

Study of Macitentan (ACT-064992) on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension

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