Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
- Conditions
- Systemic SclerosisUlcers
- Interventions
- Registration Number
- NCT01474109
- Lead Sponsor
- Actelion
- Brief Summary
The DUAL-1 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.
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 289
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description macitentan 10mg macitentan 10mg macitentan 10mg tablet once daily placebo placebo matching placebo once daily macitentan 3mg macitentan 3mg macitentan 3mg tablet once daily
- Primary Outcome Measures
Name Time Method Incidence Rate of New Digital Ulcers (DUs) up to Week 16 Baseline to week 16 DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Incidence rate is adjusted for 16 weeks of observation, hence is calculated as the number of new DUs/total number of observation days.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With at Least One DU Complication Up to approximately 90 weeks DU complications were defined as any one of the following, resulting from DU worsening: critical ischemic crisis necessitating hospitalization; gangrene, (auto)amputation; failure of conservative management; surgical and chemical sympathectomy, vascular reconstructions, or any unplanned surgery in the management of hand SSc manifestations; use of parenteral prostanoids; use of endothelin-receptor antagonists; class II, III, or IV narcotics or a \> 50% increase in the existing dose compared with baseline; initiation of systemic antibiotics for the treatment of infection attributed to DUs.
Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16 Baseline to week 16 HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function). Hand functionality was assessed using a composite of 4 domains (dressing and grooming, grip, hygiene, and eating).
Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16 Baseline to week 16 HAQ-DI assesses functional ability regarding fine movements of the upper extremities, locomotor activities in the lower extremities, and movements of the upper and lower limbs. Responses were extracted from the Scleroderma Health Assessment Questionnaire covering 8 domains of functional disability (dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other daily activities). A mean score ranging from 0-3 was calculated for each domain, and a composite score by dividing the summed domain scores by the number of domains. The composite score was interpreted as 0 (no impairment in function) to 3 (maximal impairment of function).
Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16 Baseline to week 16 Patients were asked to answer 24 questions on the use of the hand(s) affected by DUs over the past 7 days on a 6-point scale from 0 (yes without difficulty) to 5 (impossible). The HDISS-DU score is the arithmetic mean of the valid non-missing items. The scores are interpreted as 1 (better ability in completing activities) to 6 (worst ability in completing activities)
Percentage of Participants Without a New DU Up To Week 16 Baseline to week 16 DUs were assessed at each visit starting with the screening visit. Only DUs from the proximal interphalangeal joint (PIP) distally (both on the dorsal and volar surface of the hand, including the digital tip) were recorded. The location of each DU was noted. At each subsequent visit the location of each new DU was noted. DUs that occurred and healed between visits and were reported by patients were not recorded as new DUs. The evaluation was performed by an experienced physician or a trained rater with expertise in the assessment of DUs in systemic sclerosis (SSc). For a given patient, DUs were assessed by the same rater at each visit, whenever possible. Any DU that developed over a previously healed ulcer was recorded as a new DU. Numbers of patients with no new DU at Week 16 are imputed using the last observation carried forward method.
Trial Locations
- Locations (77)
Shanahan Rheumatology and Immunotherapy, PLLC
🇺🇸Raleigh, North Carolina, United States
Michigan State University
🇺🇸Grand Rapids, Michigan, United States
University of Medicine & Dentistry of New Jersey, UMDNJ Scleroderma Program
🇺🇸New Brunswick, New Jersey, United States
The Center for Rheumatology
🇺🇸Albany, New York, United States
Mount Sinai Hospital
🇨🇦Toronto, Ontario, Canada
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Bispebjerg Hospital København
🇩🇰Copenhagen, Denmark
Debreceni Egyetem Orvos- és Egészségtudományi Centrum
🇭🇺Debrecen, Hungary
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"
🇷🇺Ekaterinburg, Russian Federation
CHUS Hopital Fleurimont
🇨🇦Sherbrooke, Quebec, Canada
Healthcare Institution "Minsk City Hospital #1"
🇧🇾Minsk, Belarus
Faculty Hospital Hradec Králové
🇨🇿Hradec Králové, Czech Republic
Centro de Estudios Clinicos V
🇨🇱Vina del Mar, Chile
Klinički bolnički centar Split
🇭🇷Split, Croatia
Advance Rheumatology Clinic
🇮🇳Hyderabad, India
Healthcare Institution "Minsk Clinical Hospital #9"
🇧🇾Minsk, Belarus
Private Office Marta Aliste
🇨🇱Santiago, Chile
Klinicki Bolnicki Centar Osijek
🇭🇷Osijek, Croatia
Revmatologický ústav Praha
🇨🇿Praha, Czech Republic
Centralny Szpital Kliniczny MSWiA
🇵🇱Warszawa, Poland
State Healthcare Institution "Penza Regional Clinical Hospital named after N.N. Burdenko"
🇷🇺Penza, Russian Federation
Vladimir Regional State Institution of Healthcare, "Regional Clinical Hospital"
🇷🇺Vladimir, Russian Federation
Lviv Regional Clinical Hospital
🇺🇦Lviv, Ukraine
Hospital San Juan de Dios
🇨🇱Santiago, Chile
Medicity S.A.S.
🇨🇴Bucaramanga, Colombia
MHAT "Sv. Ivan Rilski" EAD Sofia - Clinic of Rheumatology
🇧🇬Sofia, Bulgaria
Christian Medical College
🇮🇳Vellore, India
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdańsk, Poland
Internal disease chair of Ukrainian medical dentist academy based on therapy department of Poltava Poltava City Clinical Hospital #1
🇺🇦Poltava, Ukraine
Budai Irgalmasrendi Kórház
🇭🇺Budapest, Hungary
Prosalud
🇨🇱Santiago, Chile
Servimed E.U.
🇨🇴Bucaramanga, Colombia
University Hospital Centre Rijeka
🇭🇷Rijeka, Croatia
Lekarna FN Brno
🇨🇿Brno, Czech Republic
Helsingin yliopistollinen keskussairaala (HYKS), Meilahden kolmiosairaala, Reumatologian klinikka
🇫🇮Helsinki, Finland
Municipal Institution of Kyiv Regional Council, Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
St. Paul's Hospital
🇨🇦Vancouver, British Columbia, Canada
Odense Universitetshospital
🇩🇰Odense, Denmark
Sarasota Arthritis Research Center
🇺🇸Sarasota, Florida, United States
The Johns Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
St Vincent's Hospital
🇦🇺Fitzroy, Australia
Medizinische Universitätsklinik Freiburg, Abt. Rheumatologie und klinische Forschung
🇩🇪Freiburg, Germany
Klinik und Poliklinik für Dermatologie und Venerologie der Universität zu Köln
🇩🇪Koln, Germany
Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
🇩🇪Berlin, Germany
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Asklepios Westklinikum Hamburg Abteilung für Gefäßmedizin, Angiologie und Diabetologie
🇩🇪Hamburg, Germany
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Royal Adelaide Hospital
🇦🇺Adelaide, Australia
MHAT "Kaspela" EOOD Plovdiv - Rheumatology Ward
🇧🇬Plovdiv, Bulgaria
Wesley Hospital, Thoracic Department
🇦🇺Auchenflower, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, Australia
Klinicka Bolnica "Svety Duh"
🇭🇷Zagreb, Croatia
Klinička bolnica Dubrava
🇭🇷Zagreb, Croatia
Gomel Regional Clinical Hospital
🇧🇾Gomel, Belarus
Multiprofile Hospital for Active Treatment "Sveti Pantaleymon"
🇧🇬Pleven, Bulgaria
Klinik für Dermatologie und Allergologie der Ruhr-Universität Bochum
🇩🇪Bochum, Germany
Azienda Ospedaliera Careggi
🇮🇹Firenze, Italy
Complesso Integrato Columbus
🇮🇹Rome, Italy
Akademie für Gefäßkrankheiten eV.
🇩🇪Karlsbad, Germany
Pécsi Tudományegyetem Klinikai Központ, Reumatológiai és Immunológiai Klinika
🇭🇺Pécs, Hungary
NZOZ Reumed
🇵🇱Lublin, Poland
Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu
🇵🇱Wrocław, Poland
St. Joseph's Health Care
🇨🇦London, Ontario, Canada
Azienda Ospedaliera Policlinico di Modena
🇮🇹Modena, Italy
Universitäts-Hautklinik Tübingen
🇩🇪Tuebingen, Germany
Dinpropetrovsk Regional Clinical Hospital named after I. Mechnykova
🇺🇦Dnipropetrovsk, Ukraine
Krishna Institute of Medical Sciences
🇮🇳Secunderabad, India
Menzies Research Institute
🇦🇺Hobart, Australia
UCLA Medical School - Rheumatology Division Rehabilitation Center
🇺🇸Los Angeles, California, United States
Arthritis & Rheumatic Disease Specialties
🇺🇸Aventura, Florida, United States
Altoona Center for Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh Department of Rheumatology
🇺🇸Pittsburgh, Pennsylvania, United States
University of Arizona Arthritis Center
🇺🇸Tucson, Arizona, United States
Rheumatologie, klinische Immunologie, Nephrologie Asklepios Rheumazentrum Hamburg Asklepios Klinik Altona
🇩🇪Hamburg, Germany
University of Michigan - Scleroderma Program
🇺🇸Ann Arbor, Michigan, United States
Rheumatology Research Associates
🇨🇦Edmonton, Alberta, Canada