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

September 10, 2015 updated by: Actelion

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

742

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1093AAS
        • Fundacion Favaloro
      • Buenos Aires, Argentina
        • Hospital Britanico
      • Buenos Aires, Argentina
        • Sanatorio Mitre
      • Buenos Aires, Argentina
        • Sanatorio Otamendi y Miroli
      • Cordoba, Argentina
        • Htal Italiano Cordoba
      • Cordoba, Argentina
        • Htla privado de Cordoba
      • Corrientes, Argentina
        • Instituto Cardiologia Corrientes
      • Santa Fe, Argentina
        • 'Hospital Italiano - Garibaldi de Rosario
  • Australia
      • Darlinghurst, NSW, Australia, 2010
        • St. Vincent's Hospital
      • Melbourne, VIC, Australia, 3181
        • The Alfred Hospital
      • Sunshine Coast, Australia, 4558
        • Royal Brisbane Hospital
  • Austria
      • Vienna, Austria
        • Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology
  • Belarus
      • Minsk, Belarus, 220036
        • Republican reserach - Pratical Centre of Cardilogy
      • Minsk, Belarus, 223040
        • Minsk Regional Clinical Hospital
      • Vitebsk, Belarus, 210037
        • Vitebsk Regional Clinical Hospital
  • Belgium
      • Leuven, Belgium
        • University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie
  • Bulgaria
      • Sofia, Bulgaria, 1309
        • Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology
  • Canada
      • Calgary, Canada
        • Peter Lougheed Centre
      • Toronto, Canada
        • Toronto General Hospital
      • Vancouver, Canada, V6Z 1Y6
        • Vancouver General Hospital
    • Ontario
      • London, Ontario, Canada
        • London Health Sciences Centre / Victoria Hospital
    • Quebec
      • Saint-Foy, Quebec, Canada
        • L'Hopital Laval
  • Chile
      • Santiago, Chile
        • Hospital San Juan de Dios
      • Santiago de Chile, Chile
        • 'Pontificia Universidad Catolica de Chile
      • Santiago de Chile, Chile
        • Hospital del Torax
  • China
      • Beijing, China, 100029
        • Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department
      • Beijing, China, 100032
        • Peking Union Medcical College Hospital, Rheumatology Department
      • Beijing, China, 100853
        • Chinese PLA General Hospital (301 Hospital), Cardiology Department
      • Shanghai, China, 200001
        • Renji Hospital, Rheumatology Dept
      • Shanghai, China, 200032
        • Zhongshan Hospital Fudan University, Cardiology Dept
      • Shanghai, China, 200127
        • Renji Hospital, Cardiology Dept
      • Shanghai, China, 200433
        • Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Guangdong General Hospital, Cardiology Department
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Jiangsu Province Hospital - Pneumology Department
  • Colombia
      • Bogota, Colombia
        • Fundación Clínica Shaio
      • Floridablanca, Santander, Colombia
        • 'Fundacion Cardiovascular de Colombia
  • Croatia
      • Rijeka, Croatia, 51 000
        • Clinical Hospital Center
  • France
      • Clamart, France, 92140
        • Hôpital Antoine Béclère / Service de Pneumologie
      • Montpellier Cedex 5, France, 34295
        • Hopital Arnaud de Villeneuve Service des Maladies Respiratoires
      • Pessac, France, 33604
        • Hopital Haut-Leveque - Maison du Haut-Leveque
  • Germany
      • Berlin, Germany
        • Unfallkrankenhaus Berlin, Klinik für Innere Medizin
      • Dresden, Germany, D-01307
        • Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
      • Giessen, Germany, D-35392
        • Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med.
      • Greifswald, Germany, D-17487
        • Universität Greifswald / Klinik für Innere Medizin B,
      • Hamburg, Germany, D-20246
        • Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie
      • Heidelberg, Germany, D-69126
        • Thoraxklinik am Universitatsklinikum Heidelberg
      • Homburg/Saar, Germany, D-66421
        • Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V
      • Koln, Germany, D-50924
        • Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie
      • Leipzig, Germany, 04103
        • Universtätsklinik Leipzig
      • Mainz, Germany, D-55131
        • Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik
      • Munich, Germany, D-81377
        • Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie
      • Regensburg, Germany, 93053
        • Universitätsklinikum Regensburg / Innere Medizin II
  • Hong Kong
      • Hong Kong, Hong Kong
        • Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics
      • Hong Kong, Hong Kong
        • Queen Mary Hospital / Division of Cardiology, Department of Medicine
  • Hungary
      • Budapest, Hungary, H-1096
        • Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)
      • Budapest, Hungary, H-1125
        • Semmelweis University, Pulmonolgy Clinic
      • Szeged, Hungary
        • University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center
  • India
      • Ahmedabad, India, 382428
        • Life Care Institute of Medical Science & Research, Ahmedabad
      • Delhi, India, 110049
        • G B Pant Hospital & Maulana Azad Medical College
      • Hyderabad, India, 500001
        • Care hospital
      • Mumbai, India, 400 012
        • King Edward VII Memorial Hospital (KEM) Hospital
      • Mumbai, India, 400016
        • P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine
      • Pune, India, 411 004
        • Deenanath Mangeshkar Hospital and Research Centre
  • Israel
      • Haifa, Israel, 34362
        • Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division
      • Petach - Tikvah, Israel, 49100
        • Rabin Medical Center - Belinson campus - Pulmonary Institute
      • Rehovot, Israel, 76100
        • Pulmonary Institute, Kaplan Medical Center
      • Tel Hashomer, Israel, 52621
        • The pulmonary institute Sheba Medical centre
      • Tel-Aviv, Israel, 64239
        • Sourasky Medical Center - Division of Pulmonary Medicine and Allergy
  • Italy
      • Roma, Italy, 00161
        • Policlinico Umberto I, Cardiologia
  • Malaysia
      • Kuala Lumpur, Malaysia, 50400
        • Institut Jantung Negara (National Heart Institute)
  • Mexico
      • Mexico City, Mexico, 14080
        • 'Instituto Nacional de Cardiología (INC) Ignacio Chávez
      • Monterrey Nuevo León, Mexico, 64020
        • Unidad de Investigación Clinica en Medicina, SC
  • Netherlands
      • Nieuwegein, Netherlands, 3435 CM
        • St. Antonius Ziekenhuis
  • Norway
      • Oslo, Norway, N0514
        • Aker University Dept of Cardilogy
  • Peru
      • Lima, Peru
        • Hospital Alberto Sabogal Sologuren - EsSALUD
      • Lima, Peru
        • IInstituto de Enfermedades Respiratorias, Clinica San Gabriel
  • Poland
      • Krakow, Poland, 31-202
        • Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ
      • Warszawa, Poland, 01-138
        • Klinika Chorób Wewnętrznych Klatki Piersiowej
      • Zabrze, Poland, 41-800
        • III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego
  • Romania
      • Bucharest, Romania, 022328
        • Institutul de boli cardiovasculare / Clinica de Cardiologie
      • Bucharest, Romania, 50159
        • Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie
  • Russian Federation
      • Ekaterinburg, Russian Federation, 620102
        • Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)
      • Kemerovo, Russian Federation, 650002
        • Municipal Health Care Institution "Kemerovo Cardiology Dispensary"
      • Moscow, Russian Federation, 105077
        • Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"
      • Moscow, Russian Federation, 117049
        • State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"
      • Moscow, Russian Federation, 121552
        • Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"
      • St. Petersburg, Russian Federation, 194156
        • Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology
      • St. Petersburg, Russian Federation, 197 022
        • State Educational Institution of High Professional Education
      • Tomsk, Russian Federation, 634063
        • State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch
      • Tomsk, Russian Federation, 634063
        • Tomsk Regional Clinical Hospital / Pulmonology Unit
      • Yaroslavl, Russian Federation, 150 003
        • Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"
  • Serbia
      • Belgrade, Serbia, 11000
        • University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA)
      • Belgrade, Serbia, 11000
        • University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis
      • Belgrade, Serbia, 11080
        • Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology
  • Singapore
      • Singapore, Singapore, 168752
        • National University Hospital/ The Heart Institute
      • Singapore, Singapore, 168752
        • Singapore General Hospital
  • Slovakia
      • Bratislava, Slovakia, 833 48
        • National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation
      • Bratislava, Slovakia, 833 48
        • Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology
  • South Africa
      • Johannesburg, South Africa, 2000
        • Netcare Milpark Hospital,Center for Chest Disease
      • Johannesburg, South Africa, 27-11-033 8197
        • Chris Hani Baragwanath Hospital, Department of Cardiology
      • Parow, South Africa, 7505
        • TREAD Research
      • Somerset West, South Africa, 7130
        • Block 4, Vergelegen Medi-Clinic
  • Spain
      • A Coruna, Spain, 15006
        • Hospital Juan Canalejo Servicio de Neumología
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General
      • Barcelona, Spain, 08036
        • Hospital Clínico I Provincial, Servicio de Neumología.
      • Madrid, Spain, 20841
        • Hospital 12 Octubre/ Cardiology department Planta 5a.
      • Malaga, Spain, 29010
        • Hospital Clínico Virgen de la Victoria / Pneumology Unit,
      • Pontevedra, Spain, 36771
        • Hospital Montecelo, Servicio de Neumología
  • Sweden
      • Lund, Sweden, SE-221 85
        • University Hospital in Lund, Heart and Lung Division
      • Uppsala, Sweden, 751 85
        • Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar
  • Taiwan
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology
      • Taipei, Taiwan
        • National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department
  • Thailand
      • Bangkok, Thailand, 10400
        • Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,
      • Bangkok, Thailand, 10700
        • Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University
      • Chiang Mai, Thailand
        • Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University
      • Khon Kaen, Thailand, 40002
        • Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University
  • Turkey
      • Istanbul, Turkey
        • Istanbul University Cardiology Institure
  • Ukraine
      • Dnepropetrovsk, Ukraine, 49060
        • Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid
      • Lviv, Ukraine, 79010
        • Danylo Halytskyi Lviv State Medical University
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Royal Free Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35249-0001
        • University of Alabama at Birmingham
    • Arizona
      • Pheonix, Arizona, United States, 85013
        • Arizona Pulmonary Specialists
    • California
      • Los Angeles, California, United States
        • GLVA Healthcare Center
      • San Diego, California, United States
        • University of California, San Diego
      • Santa Barbara, California, United States
        • Santa Barbara Cottage Hospital
      • Torrance, California, United States
        • LIU Center for Pulmonary Hypertension
    • Colorado
      • Denver, Colorado, United States
        • University of Colorado Health Sciences Center
    • Florida
      • Jacksonville, Florida, United States
        • Mayo Clinic, Jacksonville
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease
      • Atlanta, Georgia, United States, 30342
        • Pulmonary & Critical Care of Atlanta
      • Decatur, Georgia, United States
        • Southeastern Lung Care
    • Illinois
      • Chicago, Illinois, United States
        • University of Chicago Hospitals
    • Iowa
      • Iowa City, Iowa, United States
        • University of Iowa
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Kentucky
      • Louisville, Kentucky, United States
        • Kentuckiana Pulmonary Associate, PLLC
    • Louisiana
      • New Orleans, Louisiana, United States
        • Medical Center of Louisiana at New Orleans
    • Maine
      • Portland, Maine, United States, 04102
        • Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States
        • Boston University School of Medicine
      • Boston, Massachusetts, United States
        • Pulmonary/Critical Care Division/Tufts New England Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States
        • University of Michigan
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • New Brunswick, New Jersey, United States
        • University of NJ - Robert Wood Johnson Medical School
    • New York
      • New York, New York, United States
        • Columbia University Medical Center - Pediatric Cardiology
    • North Carolina
      • Durham, North Carolina, United States
        • Duke University Medical Center
    • Ohio
      • Cincinnati, Ohio, United States
        • University of Cincinnati Ohio Heart Health Center
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Tennessee
      • Nashville, Tennessee, United States
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75235
        • University of Texas Medical Center - St. Paul University
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine and the Methodist Hospital
    • Utah
      • Salt Lake City, Utah, United States
        • Dept. of Pulmonary Medicine - Latter Day Saints Hospital
    • Virginia
      • Norfolk, Virginia, United States, 23507
        • Sentara Hospital T/A Sentara Cardiovascular Research Institute
    • Wisconsin
      • Milwaukee, Wisconsin, United States
        • Comprehensive Cardiovascular Care Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Macitentan (ACT-064992) tablet, 3 mg, once daily
Drug: macitentan (ACT-064992)
Tablet, 3 mg dosage, once daily
Drug: macitentan (ACT-064992)
Tablet, 10 mg dosage, once daily
Experimental: 2
Macitentan (ACT-064992) tablet, 10 mg, once daily
Drug: macitentan (ACT-064992)
Tablet, 3 mg dosage, once daily
Drug: macitentan (ACT-064992)
Tablet, 10 mg dosage, once daily
Placebo Comparator: 3
Matching placebo, once daily
Drug: placebo
Matching placebo, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
Time Frame: Up to end of treatment (data presented up to month 36)

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
Up to end of treatment (data presented up to month 36)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Death Due to PAH or Hospitalisation for PAH up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Time Frame: Up to end of treatment (data presented up to month 36)
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.
Up to end of treatment (data presented up to month 36)
Time to Death Due to Any Cause up to the End of Treatment (Kaplan-Meier Estimate of Patients Without an Event)
Time Frame: Up to end of treatment (data presented up to month 36)
Events of death due to any cause up to the end of treatment (plus 7 days)
Up to end of treatment (data presented up to month 36)
Time to Death Due to Any Cause up to the End of Study (Kaplan-Meier Estimate of Patients Without an Event)
Time Frame: Up to end of study (data presented up to month 36)
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).
Up to end of study (data presented up to month 36)
Change From Baseline to Month 6 in 6-minute Walk Distance
Time Frame: Baseline to month 6
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.
Baseline to month 6
Number of Patients With Improvements in World Health Organization Functional Class From Baseline to Month 6
Time Frame: 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.
Baseline to month 6
Pulmonary Vascular Resistance at Baseline and Month 6
Time Frame: Baseline to 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.
Baseline to month 6
Cardiac Index at Baseline and Month 6
Time Frame: Baseline to 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.
Baseline to month 6

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Summary of the First Causes of Morbidity or Mortality
Time Frame: Up to end of treatment (Up to 36 months)

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
Up to end of treatment (Up to 36 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actelion

Investigators

  • Study Chair: Loic Perchenet, PhD, Actelion

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2008

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

April 14, 2008

First Submitted That Met QC Criteria

April 16, 2008

First Posted (Estimate)

April 17, 2008

Study Record Updates

Last Update Posted (Estimate)

September 28, 2015

Last Update Submitted That Met QC Criteria

September 10, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-055-302

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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