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Systemic SclerosisPhase 3DUAL-1NCT01474109

Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients

A Phase 3 study testing macitentan 3mg and macitentan 10mg in people with Systemic Sclerosis and Ulcers, run by Actelion at 77 sites in 18 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 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systemic Sclerosis, Ulcers
What is being tested?
macitentan 3mg and macitentan 10mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
289 participants
Where
77 sitesin 18 countries
Study dates
Dec 2011to Nov 2013
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 digital ulcers (DU) at baseline
  • History of at least one additional recent active ischemic DU

Who cannot join

  • DUs due to condition other than SSc
  • Symptomatic Pulmonary arterial hypertension (PAH)
  • Body mass index (BMI) < 18 kg/m^2
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 x upper limit of the normal range (ULN)
  • Hemoglobin < 75% of the lower limit of the normal range
  • Systolic blood pressure < 95 mmHg or diastolic blood pressure < 50 mmHg
Show all 17Show fewer
  • 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 phosphodiesterase type-5 (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.

Trial locations and contacts

77 sites in 18 countries.

77 sites in 18 countries

United States15 sites

  • The Center for Rheumatology

    Albany, New York, 12206

  • University of Michigan - Scleroderma Program

    Ann Arbor, Michigan, 48109

  • Arthritis & Rheumatic Disease Specialties

    Aventura, Florida, 33180

  • The Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21224-6801

  • Medical University of South Carolina

    Charleston, South Carolina, 29425-8905

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Altoona Center for Clinical Research

    Duncansville, Pennsylvania, 16635

  • Michigan State University

    Grand Rapids, Michigan, 49546

  • UCLA Medical School - Rheumatology Division Rehabilitation Center

    Los Angeles, California, 90095

  • University of Medicine & Dentistry of New Jersey, UMDNJ Scleroderma Program

    New Brunswick, New Jersey, 08903-0010

  • Ochsner Medical Center

    New Orleans, Louisiana, 70121

  • University of Pittsburgh Department of Rheumatology

    Pittsburgh, Pennsylvania, 15261

  • Shanahan Rheumatology and Immunotherapy, PLLC

    Raleigh, North Carolina, 27617-7884

  • Sarasota Arthritis Research Center

    Sarasota, Florida, 34239

  • University of Arizona Arthritis Center

    Tucson, Arizona, 85724

Other trials in United States

Germany8 sites

  • Universitätsmedizin Berlin Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie

    Berlin, 10117

  • Klinik für Dermatologie und Allergologie der Ruhr-Universität Bochum

    Bochum, 44791

  • Klinik und Poliklinik für Dermatologie und Venerologie der Universität zu Köln

    Cologne, 50937

  • Medizinische Universitätsklinik Freiburg, Abt. Rheumatologie und klinische Forschung

    Freiburg im Breisgau, 79106

  • Asklepios Westklinikum Hamburg Abteilung für Gefäßmedizin, Angiologie und Diabetologie

    Hamburg, 22559

  • Rheumatologie, klinische Immunologie, Nephrologie Asklepios Rheumazentrum Hamburg Asklepios Klinik Altona

    Hamburg, 22763

  • Akademie für Gefäßkrankheiten eV.

    Karlsbad, 76307

  • Universitäts-Hautklinik Tübingen

    Tübingen, 72076

Other trials in Germany

Croatia6 sites

  • Klinicki Bolnicki Centar Osijek

    Osijek, 31000

  • University Hospital Centre Rijeka

    Rijeka, 51000

  • Klinički bolnički centar Split

    Split, 21000

  • Klinicka Bolnica "Svety Duh"

    Zagreb, 10000

  • Klinička bolnica Dubrava

    Zagreb, 10000

  • University Hospital Centre Zagreb

    Zagreb, 10000

Other trials in Croatia

Australia5 sites

  • Royal Adelaide Hospital

    Adelaide, 5000

  • Wesley Hospital, Thoracic Department

    Auchenflower, 4066

  • Royal Prince Alfred Hospital

    Camperdown, 2050

  • St Vincent's Hospital

    Fitzroy, 3065

  • Menzies Research Institute

    Hobart, 7000

Other trials in Australia

Canada5 sites

  • Rheumatology Research Associates

    Edmonton, Alberta, T5M 0H4

  • St. Joseph's Health Care

    London, Ontario, N6A 4V2

  • CHUS Hopital Fleurimont

    Sherbrooke, Quebec, J1H 5N4

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

Other trials in Canada

Chile4 sites

  • Prosalud

    Santiago, 7510047

  • Private Office Marta Aliste

    Santiago, 7510186

  • Hospital San Juan de Dios

    Santiago, 8500000

  • Centro de Estudios Clinicos V

    Viña del Mar, 2570017

Other trials in Chile

Poland4 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-952

  • NZOZ Reumed

    Lublin, 20-607

  • Centralny Szpital Kliniczny MSWiA

    Warsaw, 02-507

  • Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

    Wroclaw, 50-566

Other trials in Poland

Ukraine4 sites

  • Dinpropetrovsk Regional Clinical Hospital named after I. Mechnykova

    Dnipropetrovsk, 49005

  • Municipal Institution of Kyiv Regional Council, Kyiv Regional Clinical Hospital

    Kyiv, 04107

  • Lviv Regional Clinical Hospital

    Lviv, 79010

  • Internal disease chair of Ukrainian medical dentist academy based on therapy department of Poltava Poltava City Clinical Hospital #1

    Poltava, 36039

Other trials in Ukraine

Belarus3 sites

  • Gomel Regional Clinical Hospital

    Homyel, 246029

  • Healthcare Institution "Minsk City Hospital #1"

    Minsk, 220013

  • Healthcare Institution "Minsk Clinical Hospital #9"

    Minsk, 220116

Other trials in Belarus

Bulgaria3 sites

  • Multiprofile Hospital for Active Treatment "Sveti Pantaleymon"

    Pleven, 5800

  • MHAT "Kaspela" EOOD Plovdiv - Rheumatology Ward

    Plovdiv, 4002

  • MHAT "Sv. Ivan Rilski" EAD Sofia - Clinic of Rheumatology

    Sofia, 1612

Other trials in Bulgaria

Czechia3 sites

  • Lekarna FN Brno

    Brno, 62500

  • Faculty Hospital Hradec Králové

    Hradec Králové, 500 05

  • Revmatologický ústav Praha

    Prague, 12000

Other trials in Czechia

Hungary3 sites

  • Budai Irgalmasrendi Kórház

    Budapest, 1023

  • Debreceni Egyetem Orvos- és Egészségtudományi Centrum

    Debrecen, 4032

  • Pécsi Tudományegyetem Klinikai Központ, Reumatológiai és Immunológiai Klinika

    Pécs, 7632

Other trials in Hungary

India3 sites

  • Advance Rheumatology Clinic

    Hyderabad, 500082

  • Krishna Institute of Medical Sciences

    Secunderabad, 500 003

  • Christian Medical College

    Vellore, 632004

Other trials in India

Italy3 sites

  • Azienda Ospedaliera Careggi

    Florence, 50139

  • Azienda Ospedaliera Policlinico di Modena

    Modena, 41100

  • Complesso Integrato Columbus

    Rome, 00168

Other trials in Italy

Russia3 sites

  • State Healthcare Institution "Penza Regional Clinical Hospital named after N.N. Burdenko"

    Penza, 440026

  • Vladimir Regional State Institution of Healthcare, "Regional Clinical Hospital"

    Vladimir, 600023

  • State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"

    Yekaterinburg, 620102

Other trials in Russia

Colombia2 sites

  • Medicity S.A.S.

    Bucaramanga

  • Servimed E.U.

    Bucaramanga

Other trials in Colombia

Denmark2 sites

  • Bispebjerg Hospital København

    Copenhagen, 2400

  • Odense Universitetshospital

    Odense, 5000

Other trials in Denmark

Finland1 site

  • Helsingin yliopistollinen keskussairaala (HYKS), Meilahden kolmiosairaala, Reumatologian klinikka

    Helsinki, 00290

Other trials in Finland

About this study

Official title: Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel Group Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Patients With Ischemic Digital Ulcers Associated With Systemic Sclerosis

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).

Read more

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.
Read the 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.

Being tested
macitentan 3mg, macitentan 10mg, placebo
Keywords
systemic sclerosis, digital ulcers
Medical subject headings
Scleroderma, Systemic, Ulcer, digital ulcers

What participants receive

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

  • macitentan 3mgDrug

    Also called ACT-064992

    macitentan 3mg tablet once daily

  • macitentan 10mgDrug

    Also called ACT-064992

    macitentan 10mg tablet once daily

  • placeboDrug

    matching placebo once daily

Study groups in NCT01474109
Study groupRoleWhat they receive
macitentan 3mgActive comparatormacitentan 3mg tablet once daily
Receives: Drug: macitentan 3mg
macitentan 10mgActive comparatormacitentan 10mg tablet once daily
Receives: Drug: macitentan 10mg
placeboPlacebo 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. Incidence Rate of New Digital Ulcers (DUs) up 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.

    Measured: Baseline to week 16

Secondary outcomes (5)

  1. Percentage of Participants Without a New DU Up 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.

    Measured: Baseline to week 16

  2. Percentage of Participants With at Least One DU Complication

    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.

    Measured: Up to approximately 90 weeks

  3. Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From 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).

    Measured: Baseline to week 16

  4. Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From 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).

    Measured: Baseline to week 16

  5. Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From 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)

    Measured: Baseline to week 16

Timeline

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

  1. First posted18 Nov 2011 (estimated)
  2. Study startDec 2011
  3. Primary completionNov 2013
  4. Study completionNov 2013

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
289 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01474109
Sponsor's protocol ID
AC-055C301
Acronym
DUAL-1
Status last verified
Jan 2015
First submitted
31 Oct 2011
Last updated
6 Jan 2015
Data monitoring committee
Yes

Publications

  • Khanna D, Denton CP, Merkel PA, Krieg T, Le Brun FO, Marr A, Papadakis K, Pope J, Matucci-Cerinic M, Furst DE; DUAL-1 Investigators; DUAL-2 Investigators. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials. JAMA. 2016 May 10;315(18):1975-88. doi: 10.1001/jama.2016.5258.

    PubMed 27163986

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing macitentan 3mg and macitentan 10mg in people with Systemic Sclerosis and Ulcers, run by Actelion at 77 sites in 18 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 5 inclusion and 17 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 6 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in United States, Germany, Croatia, Australia, Canada and 13 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 6 Jan 2015). 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?

Incidence Rate of New Digital Ulcers (DUs) up to Week 16 (time frame: Baseline to week 16). 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 NCT01474109, which also lists 1 linked publication.

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 6 Jan 2015.

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