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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01474109




Trial ID
NCT01474109
Ethics application status
Date submitted
31/10/2011
Date registered
15/11/2011
Date last updated
2/01/2015

Titles & IDs
Public title
Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
Scientific 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
Secondary ID [1] 0 0
AC-055C301
Universal Trial Number (UTN)
Trial acronym
DUAL-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Sclerosis 0 0
Ulcers 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - macitentan 3mg
Treatment: Drugs - macitentan 10mg
Treatment: Drugs - placebo

Active Comparator: macitentan 3mg - macitentan 3mg tablet once daily

Active Comparator: macitentan 10mg - macitentan 10mg tablet once daily

Placebo Comparator: placebo - matching placebo once daily


Treatment: Drugs: macitentan 3mg
macitentan 3mg tablet once daily

Treatment: Drugs: macitentan 10mg
macitentan 10mg tablet once daily

Treatment: Drugs: placebo
matching placebo once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to week 16
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to week 16
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to approximately 90 weeks
Secondary outcome [3] 0 0
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).
Timepoint [3] 0 0
Baseline to week 16
Secondary outcome [4] 0 0
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).
Timepoint [4] 0 0
Baseline to week 16
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Baseline to week 16

Eligibility
Key inclusion criteria
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 digital ulcers (DU) at baseline

- History of at least one additional recent active ischemic DU
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria :

- 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

- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Wesley Hospital, Thoracic Department - Auchenflower
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [5] 0 0
Menzies Research Institute - Hobart
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
4066 - Auchenflower
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
3065 - Fitzroy
Recruitment postcode(s) [5] 0 0
7000 - Hobart
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
Belarus
State/province [13] 0 0
Gomel
Country [14] 0 0
Belarus
State/province [14] 0 0
Minsk
Country [15] 0 0
Bulgaria
State/province [15] 0 0
Pleven
Country [16] 0 0
Bulgaria
State/province [16] 0 0
Plovdiv
Country [17] 0 0
Bulgaria
State/province [17] 0 0
Sofia
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
British Columbia
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Chile
State/province [22] 0 0
Santiago
Country [23] 0 0
Chile
State/province [23] 0 0
Vina del Mar
Country [24] 0 0
Colombia
State/province [24] 0 0
Bucaramanga
Country [25] 0 0
Croatia
State/province [25] 0 0
Osijek
Country [26] 0 0
Croatia
State/province [26] 0 0
Rijeka
Country [27] 0 0
Croatia
State/province [27] 0 0
Split
Country [28] 0 0
Croatia
State/province [28] 0 0
Zagreb
Country [29] 0 0
Czech Republic
State/province [29] 0 0
Brno
Country [30] 0 0
Czech Republic
State/province [30] 0 0
Hradec Králové
Country [31] 0 0
Czech Republic
State/province [31] 0 0
Praha
Country [32] 0 0
Denmark
State/province [32] 0 0
Copenhagen
Country [33] 0 0
Denmark
State/province [33] 0 0
Odense
Country [34] 0 0
Finland
State/province [34] 0 0
Helsinki
Country [35] 0 0
Germany
State/province [35] 0 0
Berlin
Country [36] 0 0
Germany
State/province [36] 0 0
Bochum
Country [37] 0 0
Germany
State/province [37] 0 0
Freiburg
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Germany
State/province [39] 0 0
Karlsbad
Country [40] 0 0
Germany
State/province [40] 0 0
Koln
Country [41] 0 0
Germany
State/province [41] 0 0
Tuebingen
Country [42] 0 0
Hungary
State/province [42] 0 0
Budapest
Country [43] 0 0
Hungary
State/province [43] 0 0
Debrecen
Country [44] 0 0
Hungary
State/province [44] 0 0
Pécs
Country [45] 0 0
India
State/province [45] 0 0
Hyderabad
Country [46] 0 0
India
State/province [46] 0 0
Secunderabad
Country [47] 0 0
India
State/province [47] 0 0
Vellore
Country [48] 0 0
Italy
State/province [48] 0 0
Firenze
Country [49] 0 0
Italy
State/province [49] 0 0
Modena
Country [50] 0 0
Italy
State/province [50] 0 0
Rome
Country [51] 0 0
Poland
State/province [51] 0 0
Gdansk
Country [52] 0 0
Poland
State/province [52] 0 0
Lublin
Country [53] 0 0
Poland
State/province [53] 0 0
Warszawa
Country [54] 0 0
Poland
State/province [54] 0 0
Wroclaw
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Ekaterinburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Penza
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Vladimir
Country [58] 0 0
Ukraine
State/province [58] 0 0
Dnipropetrovsk
Country [59] 0 0
Ukraine
State/province [59] 0 0
Kyiv
Country [60] 0 0
Ukraine
State/province [60] 0 0
Lviv
Country [61] 0 0
Ukraine
State/province [61] 0 0
Poltava

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT01474109
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries