AzTrials
AzTrials

Pulmonary Arterial HypertensionPhase 3SERAPHINNCT00660179

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

A Phase 3 study testing macitentan (ACT-064992) in people with Pulmonary Arterial Hypertension, run by Actelion at 153 sites in 38 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
Pulmonary Arterial Hypertension
What is being tested?
macitentan (ACT-064992)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
742 participants
Where
153 sitesin 38 countries
Study dates
May 2008to Apr 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
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  • 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).

Who cannot join

  • 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.
Show all 23Show fewer
  • 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.

Trial locations and contacts

153 sites in 38 countries.

153 sites in 38 countries

United States33 sites

  • University of Michigan

    Ann Arbor, Michigan

  • Emory University Hospital - McKelvey Center for Lung Transplantation & Pulmonary Vascular Disease

    Atlanta, Georgia, 30322

  • Pulmonary & Critical Care of Atlanta

    Atlanta, Georgia, 30342

  • University of Maryland School of Medicine

    Baltimore, Maryland, 21201

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249-0001

  • Boston University School of Medicine

    Boston, Massachusetts

  • Pulmonary/Critical Care Division/Tufts New England Medical Center

    Boston, Massachusetts

  • University of Chicago Hospitals

    Chicago, Illinois

  • University of Cincinnati Ohio Heart Health Center

    Cincinnati, Ohio

  • Ohio State University

    Columbus, Ohio, 43210

  • University of Texas Medical Center - St. Paul University

    Dallas, Texas, 75235

  • Southeastern Lung Care

    Decatur, Georgia

  • University of Colorado Health Sciences Center

    Denver, Colorado

  • Duke University Medical Center

    Durham, North Carolina

  • Baylor College of Medicine and the Methodist Hospital

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa

  • Mayo Clinic, Jacksonville

    Jacksonville, Florida

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • GLVA Healthcare Center

    Los Angeles, California

  • Kentuckiana Pulmonary Associate, PLLC

    Louisville, Kentucky

  • Comprehensive Cardiovascular Care Group

    Milwaukee, Wisconsin

  • Vanderbilt University Medical Center

    Nashville, Tennessee

  • University of NJ - Robert Wood Johnson Medical School

    New Brunswick, New Jersey

  • Medical Center of Louisiana at New Orleans

    New Orleans, Louisiana

  • Columbia University Medical Center - Pediatric Cardiology

    New York, New York

  • Sentara Hospital T/A Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • Arizona Pulmonary Specialists

    Pheonix, Arizona, 85013

  • Maine Medical Center

    Portland, Maine, 04102

  • Dept. of Pulmonary Medicine - Latter Day Saints Hospital

    Salt Lake City, Utah

  • University of California, San Diego

    San Diego, California

  • Santa Barbara Cottage Hospital

    Santa Barbara, California

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Liu Center for Pulmonary Hypertension

    Torrance, California

Other trials in United States

Germany12 sites

  • Unfallkrankenhaus Berlin, Klinik für Innere Medizin

    Berlin

  • Universität zu Köln, Medizinische Klinik III, Abteilung Kardiologie

    Cologne, D-50924

  • Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus

    Dresden, D-01307

  • Universitätsklinikums Gießen und Marburg GmbH / Medizinische Klinik und Poliklinik II, Innere Med.

    Giessen, D-35392

  • Universität Greifswald / Klinik für Innere Medizin B,

    Greifswald, D-17487

  • Universitätsklinikum Hamburg-Eppendorf / Onkologie, Hämatologie und Knochenmarktransplantation mit Sektion Pneumologie

    Hamburg, D-20246

  • Thoraxklinik am Universitätsklinikum Heidelberg

    Heidelberg, D-69126

  • Universitätskliniken des Saarlandes / Medizinische Klinik und Poliklinik, Innere Medizin V

    Homburg/Saar, D-66421

  • Universtätsklinik Leipzig

    Leipzig, 04103

  • Klinikum der Johannes Gutenberg-Universität / II. Medizinische Klinik und Poliklinik

    Mainz, D-55131

  • Medizinische Klinik und Poliklinik I der Ludwig-Maximilians-Universität München / Klinikum Großhadern, Schwerpunkt Pneumologie

    Munich, D-81377

  • Universitätsklinikum Regensburg / Innere Medizin II

    Regensburg, 93053

Other trials in Germany

Russia10 sites

  • Municipal Health Care Institution "Kemerovo Cardiology Dispensary"

    Kemerovo, 650002

  • Federal State Institution "Scientific Research Institute of Pulmonology of Roszdrav"

    Moscow, 105077

  • State Health Care Institution of Moscow "City Clinical Hospital #1 named after N. I. Pirogov"

    Moscow, 117049

  • Federal State Institution "Russian Cardiology Scientific and Production Complex of Rosmedtechnology"

    Moscow, 121552

  • Federal State Institution "Federal Center of Heart, Blood and Endocrinology named after V.A. Almazov" of Rosmedtechnology

    Saint Petersburg, 194156

  • State Educational Institution of High Professional Education

    Saint Petersburg, 197 022

  • State Institution "Scientific Research Institute of Cardiology" of Tomsk Scientific Center of RAMS, Siberian branch

    Tomsk, 634063

  • Tomsk Regional Clinical Hospital / Pulmonology Unit

    Tomsk, 634063

  • Municipal Health Care Institution "Clinical Hospital of Emergency Care named after N.V. Soloviov"

    Yaroslavl, 150 003

  • Sverdlovsk Regional Clinical Hospital # 1/ Cardiology Department (2nd Therapy Department)

    Yekaterinburg, 620102

Other trials in Russia

China9 sites

  • Beijing Anzhen Hospital of the Capital University of Medical Sciences, Cardiology Department

    Beijing, 100029

  • Peking Union Medcical College Hospital, Rheumatology Department

    Beijing, 100032

  • Chinese PLA General Hospital (301 Hospital), Cardiology Department

    Beijing, 100853

  • Guangdong General Hospital, Cardiology Department

    Guangzhou, Guangdong, 510080

  • Jiangsu Province Hospital - Pneumology Department

    Nanjing, Jiangsu, 210029

  • Renji Hospital, Rheumatology Dept

    Shanghai, 200001

  • Zhongshan Hospital Fudan University, Cardiology Dept

    Shanghai, 200032

  • Renji Hospital, Cardiology Dept

    Shanghai, 200127

  • Shanghai Pulmonary Hospital, Dept of Pulmonary Circulation

    Shanghai, 200433

Other trials in China

Argentina8 sites

  • Fundacion Favaloro

    Buenos Aires, C1093AAS

  • Hospital Britanico

    Buenos Aires

  • Sanatorio MITRE

    Buenos Aires

  • SANATORIO OTAMENDI y MIROLI

    Buenos Aires

  • Htal Italiano Cordoba

    Córdoba

  • Htla privado de Cordoba

    Córdoba

  • Instituto Cardiologia Corrientes

    Corrientes

  • 'Hospital Italiano - Garibaldi de Rosario

    Santa Fe

Other trials in Argentina

India6 sites

  • Life Care Institute of Medical Science & Research, Ahmedabad

    Ahmedabad, 382428

  • G B Pant Hospital & Maulana Azad Medical College

    Delhi, 110049

  • Care Hospital

    Hyderabad, 500001

  • King Edward VII Memorial Hospital (KEM) Hospital

    Mumbai, 400 012

  • P D Hinduja National Hospital and Medical Research Centre/ Pulmunory Medicine

    Mumbai, 400016

  • Deenanath Mangeshkar Hospital and Research Centre

    Pune, 411 004

Other trials in India

Spain6 sites

  • Hospital Juan Canalejo Servicio de Neumología

    A Coruña, 15006

  • Hospital Universitario Vall d'Hebron, Pneumology Unit, Planta Baja Hospital General

    Barcelona, 08035

  • Hospital Clínico I Provincial, Servicio de Neumología.

    Barcelona, 08036

  • Hospital 12 Octubre/ Cardiology department Planta 5a.

    Madrid, 20841

  • Hospital Clínico Virgen de la Victoria / Pneumology Unit,

    Málaga, 29010

  • Hospital Montecelo, Servicio de Neumología

    Pontevedra, 36771

Other trials in Spain

Canada5 sites

  • Peter Lougheed Centre

    Calgary

  • London Health Sciences Centre / Victoria Hospital

    London, Ontario

  • L'Hopital Laval

    Saint-Foy, Quebec

  • Toronto General Hospital

    Toronto

  • Vancouver General Hospital

    Vancouver, V6Z 1Y6

Other trials in Canada

Israel5 sites

  • Lady Davis Carmel Medical Center / Department of Cardiovascular Medicine, Pulmonary Division

    Haifa, 34362

  • Rabin Medical Center - Belinson campus - Pulmonary Institute

    Petach - Tikvah, 49100

  • Pulmonary Institute, Kaplan Medical Center

    Rehovot, 76100

  • Sourasky Medical Center - Division of Pulmonary Medicine and Allergy

    Tel Aviv, 64239

  • The pulmonary institute Sheba Medical centre

    Tel HaShomer, 52621

Other trials in Israel

South Africa4 sites

  • Netcare Milpark Hospital,Center for Chest Disease

    Johannesburg, 2000

  • Chris Hani Baragwanath Hospital, Department of Cardiology

    Johannesburg, 27-11-033 8197

  • Tread Research

    Parow, 7505

  • Block 4, Vergelegen Medi-Clinic

    Somerset West, 7130

Other trials in South Africa

Thailand4 sites

  • Ramathibodi Hospital, Mahidol University, Cardiology Unit, Department of Medicine,

    Bangkok, 10400

  • Siriraj Hospital/ Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University

    Bangkok, 10700

  • Chiang Mai Hospital / Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chiang Mai University

    Chiang Mai

  • Srinagarind Hospital/Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University

    Khon Kaen, 40002

Other trials in Thailand

Australia3 sites

  • St. Vincent's Hospital

    Darlinghurst, NSW, 2010

  • The Alfred Hospital

    Melbourne, VIC, 3181

  • Royal Brisbane Hospital

    Sunshine Coast, 4558

Other trials in Australia

Belarus3 sites

  • Republican reserach - Pratical Centre of Cardilogy

    Minsk, 220036

  • Minsk Regional Clinical Hospital

    Minsk, 223040

  • Vitebsk Regional Clinical Hospital

    Vitebsk, 210037

Other trials in Belarus

Chile3 sites

  • 'Pontificia Universidad Catolica de Chile

    Santiago, Chile

  • Hospital del Torax

    Santiago, Chile

  • Hospital San Juan de Dios

    Santiago, Chile

Other trials in Chile

France3 sites

  • Hôpital Antoine Béclère / Service de Pneumologie

    Clamart, 92140

  • Hôpital Arnaud de Villeneuve Service des Maladies Respiratoires

    Montpellier, 34295

  • Hopital Haut-Leveque - Maison du Haut-Leveque

    Pessac, 33604

Other trials in France

Hungary3 sites

  • Gottsegen György Országos Kardiológiai Intézet (Hungarian Institute of Cardiology)

    Budapest, H-1096

  • Semmelweis University, Pulmonolgy Clinic

    Budapest, H-1125

  • University of Szeged Albert Szent-Györgyi Medical and Pharmaceutical Center, Faculty of General Medicine, II. Internal Medicine Clinic, Cardiology Center

    Szeged

Other trials in Hungary

Poland3 sites

  • Klinika Chorob Serca i Naczyn Instytut Kardiologii Collegium Medicum UJ

    Krakow, 31-202

  • Klinika Chorób Wewnętrznych Klatki Piersiowej

    Warsaw, 01-138

  • III Katedra i Oddział Kliniczny Kardiologii Slaskiego Uniwersytetu Medycznego

    Zabrze, 41-800

Other trials in Poland

Serbia3 sites

  • University Children's Hospital (UNIVERZITETSKA DEČJA KLINIKA)

    Belgrade, 11000

  • University Clinical Center of Serbia / Institute for Lung Diseases and Tuberculosis

    Belgrade, 11000

  • Zemun Clinical Hospital (Kliničko-bolnički centar "Zemun" ) / Department of Cardiology

    Belgrade, 11080

Other trials in Serbia

Colombia2 sites

  • Fundación Clínica Shaio

    Bogotá

  • 'Fundacion Cardiovascular de Colombia

    Floridablanca, Santander

Other trials in Colombia

Hong Kong2 sites

  • Prince of Wales Hospital/ Division of Rheumatology, Department of Medicine & Therapeutics

    Hong Kong

  • Queen Mary Hospital / Division of Cardiology, Department of Medicine

    Hong Kong

Other trials in Hong Kong

Mexico2 sites

  • 'Instituto Nacional de Cardiología (INC) Ignacio Chávez

    Mexico City, 14080

  • Unidad de Investigación Clinica en Medicina, SC

    Monterrey Nuevo León, 64020

Other trials in Mexico

Peru2 sites

  • Hospital Alberto Sabogal Sologuren - EsSALUD

    Lima

  • IInstituto de Enfermedades Respiratorias, Clinica San Gabriel

    Lima

Other trials in Peru

Romania2 sites

  • Institutul de boli cardiovasculare / Clinica de Cardiologie

    Bucharest, 022328

  • Institutul de Pneumologie "Marius Nasta" / I. Clinica de Pneumoftiziologie

    Bucharest, 50159

Other trials in Romania

Singapore2 sites

  • National University Hospital/ The Heart Institute

    Singapore, 168752

  • Singapore General Hospital

    Singapore, 168752

Other trials in Singapore

Slovakia2 sites

  • National Institute of Cardiovascular Diseases (Národný ústav srdcových a cievnych chorôb, a.s. - NÚSCH) / Department of Heart Transplantation

    Bratislava, 833 48

  • Slovak Medical University (Slovenská zdravotnícka univerzita) / Faculty of Medical Speciality Studies (Fakulta zdravotníckych špecializačných štúdií), Department of Cardiology and Angiology

    Bratislava, 833 48

Other trials in Slovakia

Sweden2 sites

  • University Hospital in Lund, Heart and Lung Division

    Lund, SE-221 85

  • Servicio de Medicina Interna, Unidad de Hipertensión Pulmonar

    Uppsala, 751 85

Other trials in Sweden

Taiwan2 sites

  • Taichung Veterans General Hospital / Division of Allergy, Immunology and Rheumatology

    Taichung, 40705

  • National Taiwan University Hospital/ Thoracic Surgical Division, Surgical Department

    Taipei

Other trials in Taiwan

Ukraine2 sites

  • Dnipropetrovsk State Medical Academy / Regional Diagnostic Center, Department of electrophysiologic researches and anaesthesiologic aid

    Dnipro, 49060

  • Danylo Halytskyi Lviv State Medical University

    Lviv, 79010

Other trials in Ukraine

Austria1 site

  • Medical University of Vienna/ Department of Internal Medicine II, Division of Cardiology

    Vienna

Other trials in Austria

Belgium1 site

  • University Hospital Gasthuisberg / Kliniekhoofd, Interne Geneeskunde - I.G. Pneumologie

    Leuven

Other trials in Belgium

Bulgaria1 site

  • Specialized Hospital for Active Treatment of Cardio-Vascular Diseases / Department of Pediatric Cardiology

    Sofia, 1309

Other trials in Bulgaria

Croatia1 site

  • Clinical Hospital Center

    Rijeka, 51 000

Other trials in Croatia

Italy1 site

  • Policlinico Umberto I, Cardiologia

    Roma, 00161

Other trials in Italy

Malaysia1 site

  • Institut Jantung Negara (National Heart Institute)

    Kuala Lumpur, 50400

Other trials in Malaysia

Netherlands1 site

  • St. Antonius ziekenhuis

    Nieuwegein, 3435 CM

Other trials in Netherlands

Norway1 site

  • Aker University Dept of Cardilogy

    Oslo, N0514

Other trials in Norway

Turkey (Türkiye)1 site

  • Istanbul University Cardiology Institure

    Istanbul

Other trials in Turkey (Türkiye)

United Kingdom1 site

  • Royal Free Hospital

    London, NW3 2QG

Other trials in United Kingdom

About this study

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

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.

Being tested
macitentan (ACT-064992), placebo
Keywords
pulmonary arterial hypertension SERAPHIN
Medical subject headings
Pulmonary Arterial Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • macitentan (ACT-064992)Drug

    Tablet, 3 mg dosage, once daily

  • macitentan (ACT-064992)Drug

    Tablet, 10 mg dosage, once daily

  • placeboDrug

    Matching placebo, once daily

Study groups in NCT00660179
Study groupRoleWhat they receive
1ExperimentalMacitentan (ACT-064992) tablet, 3 mg, once daily
Receives: Drug: macitentan (ACT-064992)
2ExperimentalMacitentan (ACT-064992) tablet, 10 mg, once daily
Receives: Drug: macitentan (ACT-064992)
3Placebo comparatorMatching placebo, once daily
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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:

    1. 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

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

Secondary outcomes (7)

  1. 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.

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

  2. 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)

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

  3. 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).

    Measured: Up to end of study (data presented up to month 36)

  4. 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.

    Measured: Baseline to month 6

  5. 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.

    Measured: Baseline to month 6

  6. 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.

    Measured: Baseline to month 6

  7. 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.

    Measured: Baseline to month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2008 (estimated)
  2. Study startMay 2008
  3. Primary completionMar 2012
  4. Study completionApr 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
742 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00660179
Sponsor's protocol ID
AC-055-302
Acronym
SERAPHIN
Status last verified
Aug 2015
First submitted
14 Apr 2008
Last updated
28 Sep 2015
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23984728

  • 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.

    PubMed 35917059

  • 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.

    PubMed 35819570

  • 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.

    PubMed 31109190

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing macitentan (ACT-064992) in people with Pulmonary Arterial Hypertension, run by Actelion at 153 sites in 38 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 153 sites in United States, Germany, Russia, China, Argentina and 33 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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) (time frame: Up to end of treatment (data presented up to month 36)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00660179, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2015.

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