Prevention and Treatment of Digital Ulcers in Systemic Sclerosis

marco matucci cerinic

Status: Unknown

Conditions: Ulcer; Systemic Sclerosis

Study type: Observational

Funder types: Other

Identifiers

NCT01836263

HEALTH-F5-2012-305495-OT1

Details and patient eligibility

About

Systemic sclerosis is an orphan, multiorgan disease affecting the connective tissue of the skin and several internal organs.

Digital ulcers are frequent and have a major impact on the quality of life in patients with systemic sclerosis. The etiology of digital ulcers is complex and multifactorial and the principal mechanisms underlying the digital ulcers formation are ischemic, mechanic and inflammatory, alone or in combination, on the basis of the systemic sclerosis vasculopathy. Consequently, there are at least three types of DU: (i) those localized at the tips of the fingers and toes, mainly resulting from an ischemic process, (ii) those localized on the dorsal aspect of the fingers where the skin retraction due to fibrosis over bony prominences seems to be the main cause, and (iii) those evolving on a pitting scar or subcutaneous calcinosis due to a combined irritative-inflammatory mechanism. An early therapy to prevent or rapidly heal digital ulcers is today considered a mandatory approach to maintain quality of life and spare the enormous costs due to conventional digital ulcer management.

This observational trial is part of the collaborative project "DeSScipher", one out of five observational trials to decipher the optimal management of systemic sclerosis.

Aim of this observational trial is:

1. To identify the best treatment combination for prevention of digital ulcers in patients with fulfilment of the new ACR/EULAR SSc criteria or the preliminary VEDOSS criteria for very early diagnosis of systemic sclerosis
2. To identify the best treatment associated with improved healing of digital ulcers in patients with fulfilment of the new ACR/EULAR SSc criteria

Thus, the observational trial consist of a prevention arm and a healing arm.

Enrollment: 420 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Juvenile and adult patients with diagnosis of systemic sclerosis according to the ACR/EULAR SSc criteria or the PRES/ACR/EULAR juvenile SSc criteria for enrollment into the prevention and healing arm
• Patients with fulfilment of the preliminary criteria for very eary diagnosis of systemic sclerosis (VEDOSS criteria) for enrollment into the prevention arm

Patients with active digital ulcers will be allocated into the healing arm. Patients without previous or history of digital ulcers (but currently without active digital ulcers) will be allocated into the prevention arm.

Definition of digital ulcers (DU): DU are 1) loss of tissue, 2) DU derived from digital pitting scars and 3) DU derived from calcinosis.

IN THIS STUDY WE CONSIDER ONLY DU (1) LOSS OF TISSUE. THE OTHER DU (2) and DU (3) ARE REGISTERED IN THE DATA BASE IF THEY ARE PRESENT, BUT ARE EXCLUDED FROM EVALUATION.

Trial design

420 participants in 4 patient groups

Prevention arm: CCB & i.v. iloprost

Description:

prevention arm: patients receiving a combination of calcium channel blockers (CCB) and concomitant i.v. iloprost (i.v. iloprost at least in the last three months)

Prevention arm: bosentan & sildenafil

Description:

prevention arm: patients receiving a combination of the endothelin receptor antagonist bosentan and the Phosphodiesterase-5 inhibitor sildenafil

Healing arm: CCB & i.v. iloprost

Description:

healing arm: patients receiving a combination of calcium channel blockers (CCB) and concomitant i.v. iloprost (i.v. iloprost at least in the last three months)

Healing arm: bosentan & sildenafil

Description:

healing arm: patients receiving a combination of the endothelin receptor antagonist bosentan and the Phosphodiesterase-5 inhibitor sildenafil