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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01474122




Registration number
NCT01474122
Ethics application status
Date submitted
31/10/2011
Date registered
18/11/2011
Date last updated
4/02/2025

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-055C302
Universal Trial Number (UTN)
Trial acronym
DUAL-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Digital Ulcers 0 0
Condition category
Condition code
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
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

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

Active comparator: Macitentan 3 mg - Oral macitentan 3 mg, once daily

Active comparator: Macitentan 10 mg - Oral macitentan 10 mg, once daily

Placebo comparator: Placebo - Oral placebo, once daily


Treatment: Drugs: Macitentan 3 mg
Macitentan 3-mg tablet once daily

Treatment: Drugs: Macitentan 10 mg
Macitentan 10-mg tablet once daily

Treatment: Drugs: Placebo
Placebo tablet matching macitentan tablet, 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
Assessment method [1] 0 0
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
Assessment method [1] 0 0
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
Assessment method [2] 0 0
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 95 weeks
Secondary outcome [3] 0 0
Change in Hand Functionality Health Assessment Questionnaire - Disability Index (HAQ-DI) Hand Component From Baseline to Week 16
Assessment method [3] 0 0
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
Assessment method [4] 0 0
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
Assessment method [5] 0 0
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 DU at baseline
* History of at least one additional recent active ischemic digital ulcer
Minimum age
18 Years
Maximum age
No limit
Sex
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 normal (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-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 endothelin receptor antagonists (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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2014
Sample size
Target
Accrual to date
Final
265
Recruitment in Australia
Recruitment state(s)

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

TypeCitations or Other Details
Journal Khanna D, Denton CP, Merkel PA, Krieg T, Le Brun F... [More Details]

Results are available at https://clinicaltrials.gov/study/NCT01474122