Clinical trial NCT01836263: Prevention and Treatment of Digital Ulcers in Systemic Sclerosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Systemic Sclerosis
Ulcer
Lead sponsor: University of Florence
Sponsor class: OTHER
Collaborators: name: European Union
name: University of Giessen
name: University of Zurich
name: University of Paris 5 - Rene Descartes
name: University of Campania Luigi Vanvitelli
name: University of Basel
name: University College, London
name: Charite University, Berlin, Germany
name: University of Pecs
name: University of Leeds
name: Schoen Klinik Hamburg Eilbek
First posted: 2013-04-19
Enrollment: 420
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population are adult and juvenile systemic sclerosis patients from the EUSTAR cohort (MEDSonline database), the VEDOSS cohort and the jSScWG cohort

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Prevention arm: Number of new digital ulcers
timeFrame: 24 months
measure: Healing arm: Time to healing of manifest digital ulcers
timeFrame: 24 months
Secondary outcomes:
measure: Prevention arm: Time to development of new digital ulcers
timeFrame: 24 months
measure: Healing arm: Number of healed digital ulcers
timeFrame: 24 months
Other outcomes:
measure: Prevention arm: novel composite digital ulcer prediction score
timeFrame: 24 months
measure: Healing arm: novel composite outcome score for the assessment of worsening of digital ulcers despite treatment
timeFrame: 24 months
Locations:
city: Paris
country: France
facility: Université Paris Descartes, Hôpital Cochin, Service de Rhumatologie A & INSERM 1016
city: Bad Nauheim
country: Germany
facility: Justus-Liebig-University Gießen, Kerckhoff Clinic, Departement of Rheumatology and Clinical Immunology
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Charité Centrum 12 für Innere Medizin und Dermatologie, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
city: Hamburg
country: Germany
facility: Centre for Pediatric Rheumatology, Klinikum Eilbek
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem - University of Pecs
city: Firenze
country: Italy
facility: University of Florence, Denothe Centre, Division of Rheumatology AOUC, Department of Biomedicine
city: Napoli-Italia
country: Italy
facility: Policlinico, Via Pansini
city: Basel
country: Switzerland
facility: Felix-Platter Spital, University of Basel
city: Zurich
country: Switzerland
facility: University of Zurich, Department of Rheumatology
city: Leeds
country: United Kingdom
facility: The Universitiy of Leeds, Division of Rheumatic and Musculoskeletal Disease, St James's University Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital, University College London
Study officials:
affiliation: University of Florence, Denothe Centre, Division of Rheumatology AOUC, Department of Biomedicine
name: Marco Matucci-Cerinic, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Universitiy of Leeds, Division of Rheumatic and Musculoskeletal Disease, St James's University Hospital
name: Francesco Del Galdo, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Justus-Liebig-University Gießen, Kerckhoff Clinic, Departement of Rheumatology and Clinical Immunology
name: Ulf Müller-Ladner, Prof.
role: STUDY_CHAIR
References:
citation: Blagojevic J, Bellando-Randone S, Abignano G, Avouac J, Cometi L, Czirjak L, Denton CP, Distler O, Frerix M, Guiducci S, Huscher D, Jaeger VK, Lorand V, Maurer B, Nihtyanova S, Riemekasten G, Siegert E, Tarner IH, Vettori S, Walker UA, Allanore Y, Muller-Ladner U, Del Galdo F, Matucci-Cerinic M; EUSTAR co-workers. Classification, categorization and essential items for digital ulcer evaluation in systemic sclerosis: a DeSScipher/European Scleroderma Trials and Research group (EUSTAR) survey. Arthritis Res Ther. 2019 Jan 24;21(1):35. doi: 10.1186/s13075-019-1822-1.