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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01474109
Registration number
NCT01474109
Ethics application status
Date submitted
31/10/2011
Date registered
18/11/2011
Date last updated
6/01/2015
Titles & IDs
Public title
Macitentan for the Treatment of Digital Ulcers in Systemic Sclerosis Patients
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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
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Secondary ID [1]
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AC-055C301
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Universal Trial Number (UTN)
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Trial acronym
DUAL-1
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Systemic Sclerosis
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Ulcers
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Condition category
Condition code
Inflammatory and Immune System
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Autoimmune diseases
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Skin
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Dermatological conditions
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Skin
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Other skin conditions
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Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence Rate of New Digital Ulcers (DUs) up to Week 16
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline to week 16
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Secondary outcome [1]
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Percentage of Participants Without a New DU Up To Week 16
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Assessment method [1]
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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.
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Timepoint [1]
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Baseline to week 16
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Secondary outcome [2]
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Percentage of Participants With at Least One DU Complication
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Assessment method [2]
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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.
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Timepoint [2]
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Up to approximately 90 weeks
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Secondary outcome [3]
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Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16
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Assessment method [3]
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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).
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Timepoint [3]
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Baseline to week 16
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Secondary outcome [4]
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Health Assessment Questionnaire - Disability Index (HAQ-DI) Overall Score From Baseline to Week 16
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Assessment method [4]
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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).
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Timepoint [4]
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Baseline to week 16
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Secondary outcome [5]
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Change in Hand Functionality - Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) Score From Baseline to Week 16
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Assessment method [5]
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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)
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Timepoint [5]
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Baseline to week 16
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/12/2011
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/11/2013
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Sample size
Target
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Accrual to date
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Final
289
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Recruitment in Australia
Recruitment state(s)
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Recruitment hospital [1]
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Royal Adelaide Hospital - Adelaide
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Recruitment hospital [2]
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Wesley Hospital, Thoracic Department - Auchenflower
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Royal Prince Alfred Hospital - Camperdown
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St Vincent's Hospital - Fitzroy
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Recruitment hospital [5]
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Menzies Research Institute - Hobart
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5000 - Adelaide
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Recruitment postcode(s) [2]
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4066 - Auchenflower
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2050 - Camperdown
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3065 - Fitzroy
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Recruitment postcode(s) [5]
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7000 - Hobart
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Recruitment outside Australia
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Funding & Sponsors
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Commercial sector/Industry
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Name
Actelion
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Ethics approval
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01474109
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01474109
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