Conditions: Digital Ulcers
Keywords: digital ulcers systemic sclerosis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 265
Healthy volunteers: no

Brief summary:
The DUAL-2 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 continue on their original randomized treatment into Period 2, until the last randomized patient has completed Period 1.

Patients are 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 (DU).

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.

Arms:
arm 1: Oral macitentan 3 mg, once daily arm 2: Oral macitentan 10 mg, once daily arm 3: Oral placebo, once daily

Interventions: intervention 1: Macitentan 3 mg intervention 2: Macitentan 10 mg intervention 3: Placebo
Intervention descriptions: intervention 1: Macitentan 3-mg tablet once daily intervention 2: Macitentan 10-mg tablet once daily intervention 3: Placebo tablet matching macitentan tablet, once daily

Protocol document: