Development and Prevention of Severe Heart Disease in Systemic Sclerosis

Systemic sclerosis is an orphan, multiorgan disease affecting the connective tissue of the skin and all internal organs. Cardiac involvement, mainly characterised by small intramyocardial coronary artery involvement and myocardial fibrosis, can cause the development of impaired diastolic ventricular filling, cardiac blocks and ventricular arrhythmias, and can ensue in congestive heart failure and sudden death. Until now, no drug has been proven to have a therapeutic effect on SSc myocardial disease on an evidence-based level. Short-term trials and retrospective studies have suggested a favourable and protective effect of calcium channel blockers and angiotensin converting enzyme inhibitors in patients with myocardial involvement. However, no data are presently available on the prevention and treatment of severe heart disease.

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 to assess the efficacy and safety of calcium channel blockers and angiotensin converting enzyme inhibitors in asymptomatic SSc patients with cardiac involvement.

Study Overview

• Status: Unknown
• Conditions: Heart Block; Systemic Sclerosis; Congestive Heart Failure; Cardiac Arrhythmia; Cardiac Diseases

• Study Type: Observational
• Enrollment (Anticipated): 765

Contacts and Locations

• Study Contact: Name: Gabriele Valentini, Prof.; Phone Number: 39815464487; Email: gabriele.valentini@unina2.it

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • Université Paris Descartes, Hôpital Cochin, Service de Rhumatologie A & INSERM 1016
    • Principal Investigator: Yannick Allanore, Prof.
• Germany
  • Bad Nauheim, Germany, 61231
    • Recruiting
    • Justus-Liebig-University Gießen, Kerckhoff Clinic, Departement of Rheumatology and Clinical Immunology
    • Principal Investigator: Ulf Müller-Ladner, Prof.
    • Sub-Investigator: Ingo H. Tarner, Dr.
    • Sub-Investigator: Marc Frerix, Dr.
  • Berlin, Germany, 10117
    • Recruiting
    • Charité Universitätsmedizin Berlin, Charité Centrum 12 für Innere Medizin und Dermatologie, Medizinische Klinik mit Schwerpunkt Rheumatologie und Klinische Immunologie
    • Principal Investigator: Gabriela Riemekasten, Prof.
  • Hamburg, Germany, 22081
    • Recruiting
    • Centre for Pediatric Rheumatology, Klinikum Eilbek
    • Principal Investigator: Ivan Foeldvari, Dr.
• Hungary
  • Pecs, Hungary, H-7622
    • Recruiting
    • Pecsi Tudomanyegyetem - University of Pecs
    • Principal Investigator: Laszlo Czirjak, Prof.
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • University of Florence, Denothe Centre, Division of Rheumatology AOUC, Department of Biomedicine
    • Principal Investigator: Marco Matucci-Cerinic, Prof.
  • Napoli-Italia, Italy, 5-80131
    • Recruiting
    • Policlinico, Via Pansini
    • Principal Investigator: Gabriele Valentini, Prof.
• Switzerland
  • Basel, Switzerland, CH 4012
    • Recruiting
    • Felix-Platter Spital, University of Basel
    • Principal Investigator: Ulrich Walker, Prof
  • Zurich, Switzerland, 8006
    • Recruiting
    • University of Zurich, Department of Rheumatology
    • Principal Investigator: Oliver Distler, Prof.
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • The Universitiy of Leeds, Division of Rheumatic and Musculoskeletal Disease, St James's University Hospital
    • Principal Investigator: Francesco Del Galdo, Dr.
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Hospital, University College London
    • Principal Investigator: Christopher Denton, Prof.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population are adult and juvenile SSc patients from the EUSTAR cohort (MEDSonline database) and the jSScWG cohort

Description

Inclusion Criteria:

• Juvenile and adult systemic sclerosis patients, with diagnosis according to the SSc ACR/EULAR criteria or the PRES/ACR/EULAR juvenile SSc criteria respectively
• Asymptomatic (for cardiac disease) systemic sclerosis patients at risk for severe heart disease with at least one of the following risk factors: male sex and/or DLCO lower than 80% and/or sPAP > 30 mmHg and/or synovitis and/or joint contractures and/or digital ulcers and/or proteinuria.

Asymptomatic for cardiac disease is defined by patients without dyspnea NYHA >/= II, without palpitations and without bilateral leg edema.

Exclusion Criteria:

• Any significant pulmonary parenchymal (FVC < 70% and/or DLCO < 70%), pulmonary vascular (estimated systolic PAP > 40 mmHg), gastrointestinal (malabsorption syndrome or paralytic ileus) or renal (serum creatinine level >1.2 mg/dl, dialysis or previous scleroderma renal crisis) involvement
• Patients with dyspnea class NYHA >/= II
• Patients with palpitations
• Patients with bilateral leg edema.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
CCB; Patients receiving calcium channel blockers (CCB)
ACEi; Patients receiving angiotensin converting enzyme inhibitors (ACEi)
CCB and ACEi; Patients receiving calcium channel blockers (CCB) and angiotensin converting enzyme inhibitors (ACEi)
No treatment; Patients not receiving calcium channel blockers (CCB) and/or angiotensin converting enzyme inhibitors (ACEi)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative incidence of CB, VA, pacemaker implantation, congestive heart failure and sudden death	Cumulative incidence of cardiac blocks, ventricular arrhythmias, pacemaker implantation, congestive heart failure and sudden death.	1 years

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of drug-related adverse events, incidence of withdrawal from treatment due to drug-related adverse events	1 year

Collaborators and Investigators

• Sponsor: Gabriele Valentini
• Collaborators: University of Pecs; Charite University, Berlin, Germany; University of Zurich; University College, London; University of Leeds; University of Basel; University of Giessen; University of Florence; European Union; University of Paris 5 - Rene Descartes; Schoen Klinik Hamburg Eilbek
• Investigators: Study Chair: Ulf Müller-Ladner, Prof., Justus-Liebig-University Gießen, Kerckhoff Clinic, Departement of Rheumatology and Clinical Immunology; Principal Investigator: Gabriele Valentini, Prof., Policlinico, Via Pansini, Napoli-Italia

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: April 8, 2013
• First Submitted That Met QC Criteria: April 8, 2013
• First Posted (Estimate): April 11, 2013

Study Record Updates

• Last Update Posted (Estimate): November 8, 2013
• Last Update Submitted That Met QC Criteria: November 7, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Skin Diseases; Connective Tissue Diseases; Cardiac Conduction System Disease; Heart Failure; Heart Diseases; Sclerosis; Heart Block; Scleroderma, Systemic; Scleroderma, Diffuse; Arrhythmias, Cardiac
• Other Study ID Numbers: HEALTH-F5-2012-305495-OT5