Trial record 1 of 1 for:    DUAL-2
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Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients (DUAL-2)

This study is currently recruiting participants.
Verified July 2013 by Actelion
Information provided by (Responsible Party):
Actelion Identifier:
First received: October 31, 2011
Last updated: July 11, 2013
Last verified: July 2013

The DUAL-2 study is designed as a multicenter, double-blind two-period study with an initial fixed 16-week Period 1, followed by a Period 2 of variable duration. All patients completing Period 1 will continue on their original randomized treatment into Period 2, until the last randomized patient has completed Period 1.

Patients will be randomized in a 1:1:1 ratio (macitentan 3mg: macitentan 10mg: placebo).

The primary objective is to demonstrate the effect of macitentan on the reduction of the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcers (DU).

Other objectives include:

  • the evaluation of the efficacy of macitentan on hand functionality and DU burden at Week 16 in SSc patients with ongoing DU disease.
  • the evaluation of the safety and tolerability of macitentan in these patients.
  • the evaluation of the efficacy of macitentan on time to first DU complication during the entire treatment period.

Condition Intervention Phase
Systemic Sclerosis
Drug: macitentan 3mg
Drug: macitentan 10mg
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Prospective, Randomized, Placebo-controlled, Double-blind, Mutlicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Schemic Digital Ulcers Associated With Systemic Sclerosis

Resource links provided by NLM:

Further study details as provided by Actelion:

Primary Outcome Measures:
  • cumulative number of digital ulcers up to week 16 [ Time Frame: Period1: baseline (visit 2) to week 16. Period2: week 16 to end of study (which will occur when the last randomized patient, not prematurely withdrawn, has completed Period 1 and a 30 day safety follow-up period) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • hand functionality assessed through HDISS-DU PRO and HAQ-DI [ Time Frame: Period1: baseline (visit 2) to week 16. Period2: week 16 to end of study (which will occur when the last randomized patient, not prematurely withdrawn, has completed Period 1 and a 30 day safety follow-up period) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 285
Study Start Date: December 2011
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: macitentan 3mg
macitentan tablet 3mg once daily
Drug: macitentan 3mg
macitentan tablet 3mg once daily
Other Name: ACT-064992
Placebo Comparator: placebo
matching placebo once daily
Drug: placebo
matching placebo once daily
Other Name: placebo
Active Comparator: macitentan 10mg
macitentan tablet 10mg once daily
Drug: macitentan 10mg
macitentan tablet 10mg once daily
Other Name: ACT-064992

Detailed Description:

Recurrent digital ulcers (DU) are a manifestation of vascular disease in patients with systemic sclerosis (SSc), are an important source of morbidity and lead to impaired function in these patients. In this study, we are investigating whether treatment with the endothelin receptor antagonist, macitentan, decreases the development of new digital ulcers in patients with SSc. Macitentan is a highly potent, tissue-targeting dual endothelin receptor antagonist. Through complete blockade of endothelin action, macitentan is expected to protect tissue from the damaging effect of elevated endothelin. This therapy is not approved for the treatment of systemic sclerosis, but the use of an ERA is an attractive approach in combating the structural vascular damage observed in SSc leading to complications such as DUs.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria :

  • Patients ≥ 18 years of age
  • Women of childbearing potential must use two reliable methods of contraception
  • Diagnosis of SSc according to the classification criteria of the American College of Rheumatology (ACR)
  • At least one visible, active ischemic DU at baseline
  • History of at least one additional recent active ischemic digital ulcers(DU)

Exclusion Criteria :

  • DUs due to condition other than SSc
  • Symptomatic PAH
  • BMI < 18 kg/m2
  • AST and/or ALT > 1.5 x ULN
  • Hemoglobin < 75% of the lower limit of the normal range
  • Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg
  • Severe malabsorption; any severe organ failure (e.g., lung, kidney), or any life-threatening condition.
  • Females who are pregnant or breastfeeding or plan to do so during the course of this study.
  • Substance or alcohol abuse or dependence, or tobacco use at any level.
  • Treatment with PDE5 inhibitors.
  • Patients on statins, who have received treatment for less than 3 months prior to Screening or whose treatment has not been stable during this period.
  • Patients on vasodilators, who have received treatment for less than 2 weeks prior to Screening or whose treatment has not been stable during this period.
  • Treatment with prostanoids within 3 months.
  • Treatment with disease modifying agents if present for less than 3 months prior to Screening or whose treatment has not been stable for at least 1 month prior to Screening.
  • Treatment with oral corticosteroids (> 10 mg/day of prednisone or equivalent).
  • Treatment with ERAs within 3 months.
  • Systemic antibiotics to treat infected DU(s) within 4 weeks.
  Contacts and Locations
Please refer to this study by its identifier: NCT01474122

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United States, California
Stanford Univ. School of Medicine - Palo Alto VA Health Care System Recruiting
Palo Alto, California, United States, 94304
Contact: Lorinda Chung    650-723-6961   
Contact: Clinical Investigator   
United States, Connecticut
University of Connecticut Health Center - Division of Rheumatic Diseases Recruiting
Farmington, Connecticut, United States, 06030-1310
Contact: Naomi Rothfield    860-679-3604   
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United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Virgina Steen   
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United States, Florida
Millennium Research Recruiting
Ormond Beach, Florida, United States, 32174
Contact: Michael Kohen   
Cleveland Clinic Florida Recruiting
Weston, Florida, United States, 33331
Contact: Hossam Elzawawy    954-659-5185   
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Florida Medical Clinic-PA Recruiting
Zephyrhills, Florida, United States, 33542
Contact: David H Sikes, MD    813-780-8368   
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United States, Illinois
Northwestern University - Feinberg School of Medicine Department of Rheumatology Recruiting
Chicago, Illinois, United States, 60611
Contact: John Varga    312-695-8628   
Contact: Clinical Investigator   
United States, Massachusetts
Boston University School of Medicine Recruiting
Boston, Massachusetts, United States, 02118-2394
Contact: Robert Simms    617-638-4306   
Contact: Clinical Investigator   
United States, Missouri
Washington University School of Medicine Recruiting
St Louis, Missouri, United States, 63110
Contact: Richard Brasington   
United States, New York
North Shore Long Island Jewish Health System - Div. of Rheumatology & Allergy-Clinical Immunology Recruiting
Lake Success, New York, United States, 11042
Contact: Avram Goldberg, MD    516-562-4392   
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The Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Robert Spiera    212-774-2403   
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United States, Ohio
Ruppert Health Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Bashar Kahaleh    419-383-4271   
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United States, Pennsylvania
The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Chris T Derk    215-615-4306   
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United States, Texas
University of Texas - Houston Medical School Recruiting
Houston, Texas, United States, 77030
Contact: Maureen Mayes    713-500-6900   
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United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Tracy M Frech    801-581-7724   
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United States, Washington
Arthritis Northwest PLLC Recruiting
Spokane, Washington, United States, 99204
Contact: Howard Kenney   
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: MaryEllen Csuka   
Centro de Educacion Medica e Investigaciones Clinicas - CEMIC Recruiting
Buenos Aires, Argentina, 4102
Contact: Alicia Eimon    54 11 4804 7500   
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Hospital Italiano de Buenos Aires Recruiting
Buenos Aires, Argentina
Contact: Luis Catoggio    011-54-4959-0200 ext 8378   
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Hospital Britanico de Buenos Aires Recruiting
Buenos Aires, Argentina, C1280AEB
Contact: Hugo Laborde    54 11 43096839   
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Sanatorio San Jose Recruiting
Caba, Argentina, C1425DUH
Contact: Cristina Beatriz Amitrano   
Hospital Privado Centro Medico de Cordoba S.A. Recruiting
Cordoba, Argentina, x5016keh
Contact: Francisco Caeiro    54 351 468 8815/8816   
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Hospital Italiano de Cordoba Recruiting
Cordoba, Argentina, X5004BAL
Contact: Alejandra Babini    54 351 410 6533   
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Clinique Universitaires Saint Luc Recruiting
Brussels, Belgium, 1200
Contact: Frédéric Houssiau    +32(0)27649390   
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Cliniques universitaires UCL Mont-Godinne Recruiting
Yvoir, Belgium, 5530
Contact: Marie Vanthuyne    +32 81 42 33 82   
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Peking Union Medical College Hospital Recruiting
Beijing, China, 100032
Contact: Xiaofeng Zeng   
Guangdong General Hospital Recruiting
Guangzhou, China, 510080
Contact: Xiao Zhang   
Renji Hospital, Shanghai Jiaotong University Recruiting
Shanghai, China, 200001
Contact: Bao Chunde   
First Affiliated Hospital of the Forth Military University Recruiting
Xi'an, China, 710032
Contact: Ping Zhu   
Hospital Pablo Tobon Uribe Recruiting
Medellin, Antioquia, Colombia
Contact: Carlos Velasquez    00574-445-9753   
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Centro Integral de Reumatologia y Inmunologia CIREI SAS Recruiting
Bogota, Colombia
Contact: Patricia Julieta Velez Sanchez    57-1-2189685   
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Fundacion Instituto du Reumatologia Fernando Chalem Recruiting
Bogota, Colombia
Contact: Philippe Chalem    57-3466432   
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Kerckhoff-Klinik GmbH Recruiting
Bad Nauheim, Germany, 61231
Contact: Walter Hermann    +49 (0) 6032 - 996 - 2101   
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Universitätsklinikum der Technischen Universität Dresden Recruiting
Dresden, Germany, 01307
Contact: Roland Aschoff    +49(0)351 458 3401   
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Hautklinik Universitätsklinikum Erlangen Recruiting
Erlangen, Germany, 91054
Contact: Michael Sticherling    +49 (0)9131 85-33851   
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Department of Dermatology University Hospital Johannes Gutenberg Recruiting
Mainz, Germany, 55131
Contact: Kerstin Steinbrink    +49 61 31 17 7130   
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Ludwig-Maximilian-Universität München Abteilung Dermatologie Recruiting
Muchen, Germany, 80337
Contact: Thomas Ruzicka    +49(0)89-5160 6001   
Contact: Clinical Investigator   
Klinik und Poliklinik für Dermatologie und Allergologie am Biderstein des Klinikums rechts der Isar der Technischen Universität München Recruiting
Muenchen, Germany, 80802
Contact: Rüdiger Hein    +49 894140-3580   
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General University Hospital LAIKO/A' Propaideftiki Pathology Clinic Recruiting
Athens, Greece, 11527
Contact: Petros Sfikakis    +302132061755   
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EUROMEDICA - Kyanos Stavros Recruiting
Thessaloniki, Greece, 54636
Contact: Lucas Settas   
General University Hospital AHEPA Recruiting
Thessaloniki, Greece, 54636
Contact: Loukas Settas    +302310-268666   
Contact: Clinical Invetigator   
Cork University Hospital Recruiting
Cork, Ireland, C1
Contact: Sinead Harney   
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Beaumont Hospital Recruiting
Dublin, Ireland, 2
Contact: Paul O'Connell    00353 878192313   
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St. Vincents University Hospital Recruiting
Dublin, Ireland, 4
Contact: Douglas Veale    +353 1277 3142   
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Mid-Western Regional Hospital Recruiting
Limerick, Ireland
Contact: Alexander Fraser    00353861744616   
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Sheba Medical Center Recruiting
Tel-Hashomer, Israel, 52621
Contact: Lidar   
Asaf Harofe Medical Center Recruiting
Zerifin, Israel, 70300
Contact: Tishler   
Unidad de Investigacion en Enfermedades Cronico Degeneratives SC Recruiting
Guadalajara, Jalisco, Mexico, 44620
Contact: Andriana Sanchez Ortiz   
Christus Muguerza del Parque Hospital Recruiting
Chihuahua, Mexico, 31000
Contact: Cesar Pacheco-Tena    52 614 4155012   
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Clinica Diagnostico y Tratamiento de las Enfermedades Reumaticas Recruiting
Distrito Federal, Mexico, 06700
Contact: Gabriel Medrano-Ramirez    01-52 55-5553-4180   
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Hospital Civil de Guadalajara - Fray Antonio Alacade Hospital No. 278 Recruiting
Guadalajara, Mexico, 44280
Contact: Sergio Gutierrez-Urena    52 33 3614 9500   
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Hospital Aranda de la Parra Leon Recruiting
Leon, Mexico, 37000
Contact: Jorge Morales-Torres    477-714-5559   
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Hospital Angeles Lindavista Recruiting
Madero, Mexico, 07760
Contact: Sandra Miriam Carrillo Vazquez    52 55 5752 4673      
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Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubrian Recruiting
Mexico D.F., Mexico, 14000
Contact: Tatiana Rodriguez    52 55 5487 0900 ext 2603   
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VU University Medical Center Recruiting
Amsterdam, Netherlands, 1081
Contact: Alexandre E Voskuyl    0031 20 444 3432   
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UMC St Radboud Recruiting
GA Nijmegen, Netherlands, 6525
Contact: Madelon Vonk    +31 24 361 45 80   
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New Zealand
Middlemore Hospital Recruiting
Auckland, New Zealand, 1640
Contact: Sunil Kumar    +64 9 2760000   
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Dunedin Hospital Recruiting
Dunedin, New Zealand, 9054
Contact: Simon Stebbing    +64 34740999 ext 8504   
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Waikato Hospital Recruiting
Hamilton, New Zealand, 3204
Contact: Kamal Solanki    +64 7 8398660 ext 94498   
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North Shore Hospital, STAR (Shore Trials and Research) Unit Recruiting
North Shore, New Zealand, 0620
Contact: Kristine Pek Ling Ng    +64 9 4868343   
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Wellington Hospital Recruiting
Wellington South, New Zealand, 7902
Contact: Richard Steele   
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Prywatna Praktyka Lekarska Prof. UM dr hab. med. Paweł Hrycaj Recruiting
Poznań, Poland, 61-397
Contact: Paweł Hrycaj    +48 61 875 08 88   
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SPSK Nr 1 PUM Szczecin Recruiting
Szczecin, Poland, 71-752
Contact: Marek Brzosko    +48 91 425 33 37   
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Wojskowy Instytut Medyczny CSK MON Recruiting
Warszawa, Poland, 04-141
Contact: Witold Tłustochowicz    +48 22 681 64 91   
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Reumatika - Centrum Reumatologii NZOZ Recruiting
Warszawa, Poland, 02-653
Contact: Anna Zubrzycka-Sienkiewicz    +48 22 378 11 17   
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SPSK Nr 1 Wrocław Recruiting
Wrocław, Poland, 50-368
Contact: Jacek Szepietowski    +48 71 784 22 88   
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Instituto Português de Reumatologia Recruiting
Lisboa, Portugal, 1050-034
Contact: Paulo Jorge Clemente Coelho    + 351 917 517 754   
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Puerto Rico
University of Puerto Rico Recruiting
San Juan, Puerto Rico, 00918
Contact: Grissel Rios    787-765-3245   
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Russian Federation
State Institution, "Institute of Rheumatology of RAMS" Recruiting
Moscow, Russian Federation, 115552
Contact: Evgeny Nasonov    +7 916 692 06 66   
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Municipal Treatment and Prevention Institution, "City Clinical Hospital #5" Recruiting
Nizhniy Novgorod, Russian Federation, 603005
Contact: Elena Grunina    +7 831 438 98 13   
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State Educational Institution of High Professional Education "Voronezh State Medical Academy named after N.N.Burdenko of Roszdrav" Recruiting
Voronezh, Russian Federation, 394036
Contact: Tatiana Chernykh    +7 903 650 82 17      
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South Africa
Groote Schuur Hospital, University of Cape Town Recruiting
Cape Town, South Africa, 7925
Contact: Asgar Kalla    +2721 404 5422   
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Louis Pasteur Medical Centre Recruiting
Pretoria, South Africa, 0001
Contact: Mahmood Ally    +27 12 3192658   
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Chris Hani Baragwanath Hospital Recruiting
Soweto, South Africa, 2013
Contact: Claudia Ickinger    +27119339377   
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HOSPITAL Universitario VALL D'HEBRON - Servicio Medicina Interna Recruiting
Barcelona, Spain, 08035
Contact: Vincent Fonollosa    : +34 93 274 63 65   
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Hospital Universitari i Politecnic La Fe Recruiting
Valencia, Spain, 46026
Contact: Jose Andres Roman    +34 96 124 4000   
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Çukurova Üniversitesi Tıp Fakültesi ROMATOLOJİ BİLİM DALI Recruiting
Adana, Turkey, 01330
Contact: Suleyman Özbek    +90 322 338 60 60   
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Dokuz Eylul Universitesi Tip Fakultesi Romatoloji Bilim Dali Recruiting
Izmir, Turkey, 35340
Contact: Melih Birlik    00902324123724   
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Municipal Healthcare Institution "Donetsk Regional Clinical Hospital of Occupational Diseases" Recruiting
Donetsk, Ukraine, 83059
Contact: Vadym Berenfus    +38 050 928 39 95   
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National scientific centre "Institute of Cardiology named after M. Strazheska" Recruiting
Kyiv, Ukraine, 03151
Contact: Volodymyr Kovalenko    +38 050 358 83 07   
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Crimean Republican Institution 'Clinical territorial medical union 'University Clinic Recruiting
Simferopol, Ukraine, 95017
Contact: Andriy Petrov    +38 050 928 39 95   
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Vinnytsia Regional Clinical Hospital named after M. Pyrogov Recruiting
Vinnytsia, Ukraine, 21018
Contact: Mykola Stanislavchuk    +38 043 257 05 72   
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Scientific and Research Institute of Handicapped Rehabilitation of Vinnitsa National Medical University named after M. Pirogova Recruiting
Vinnytsya, Ukraine, 21029
Contact: Sergiy Shevchuk    +38 066 286 65 50   
Contact: clinical investigator   
United Kingdom
Royal National Hospital Recruiting
Bath, United Kingdom, BA1 1RL
Contact: Neil McHugh    +44 1225 463223   
Contact: Clinical Investigator   
Addenbrooke's Hospital - University of Cambridge School of Clinical Medicine Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Frances Hall    +44 1223 330159   
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University Hospital Aintree - Rheumatology Department Recruiting
Liverpool, United Kingdom, L9 7AL
Contact: Marina Anderson    +44 151 529 5915   
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Royal Free & University College Medical School Recruiting
London, United Kingdom, NW3 2PF
Contact: Chris Denton    +44 20 7794 0432   
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University of Manchester School of Translational Medicine Musculoskeletal Research Group Recruiting
Manchester, United Kingdom, M13 9PT
Contact: Ariane Herrick    +44 161 206 4616   
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Ninewells Hospital & Medical School Recruiting
Scotland, United Kingdom, DD1 9SY
Contact: Jill Belch    +44 1382 632457   
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Torbay Hospital Recruiting
Torbay, United Kingdom, TQ2 7AA
Contact: Nick Viner    +44 1803654832   
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Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Actelion Identifier: NCT01474122     History of Changes
Other Study ID Numbers: AC-055C302
Study First Received: October 31, 2011
Last Updated: July 11, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
systemic sclerosis
digital ulcers

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Connective Tissue Diseases
Skin Diseases
Pathologic Processes processed this record on April 17, 2014