PI: Gabriele VALENTINI (UNINA2)
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Objectives
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Background: SSc heart disease is characterised morphologically by small intramyocardial coronary artery involvement and myocardial fibrosis involving both ventricles with a patchy distribution. It can cause the development of impaired diastolic ventricular filling (which appears to be the first detectable abnormality), CB and VA, and can ensue in CHF and SD. Short-term trials have suggested a favourable effect of CCBs and ACEi on myocardial ischemia which is thought to drive the development of myocardial fibrosis. Retrospective studies have also suggested a protective effect of CCBs on the development of a reduced left ventricular ejection fraction and of ACEi on the development of impaired diastolic ventricular filling. However, no data are presently available on the prevention and treatment of SHD.
Objective: To assess the efficacy and safety of CCBs and ACEi in asymptomatic SSc patients with cardiac involvement
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Primary endpoint
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Cumulative incidence of CB, VA, pacemaker implantation, congestive heart failure and sudden death
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Safety endpoints
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Incidence of drug-related adverse events, incidence of withdrawal from treatment due to drug-related adverse events
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Study Population
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The study population are adult and juvenile SSc patients from the EUSTAR cohort (MEDSonline database) and the jSScWG cohort.
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Inclusion criteria
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All adult and juvenile systemic sclerosis patients, with diagnosis according to the ACR/EULAR adult SSc criteria and PRES/ACR/EULAR juvenile SSc criteria respectively.
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Systemic sclerosis patients will be subdivided into 2 subgroups: 1) without and 2) with risk factors for severe heart disease (i.e. : male sex and/or DLCO/SB < 80% and/or systolic PAP > 30 mmHg and/or synovitis and/or joint contractures and/or digital ulcers and/or proteinuria).
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Exclusion criteria
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Any significant pulmonary parenchymal (FVC < 70% and/or DLCO/SB < 70%), pulmonary vascular (estimated systolic PAP > 40 mmHg), gastrointestinal (malabsorption syndrome or paralytic ileus diagnosed by physician ́s opinion) or renal (serum creatinine level >1.2 mg/dl, dialysis or previous scleroderma renal crisis) involvement.
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Patients symptomatic for cardiac disease as diagnosed by physician ́s opinion.
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Trial design
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Observational trial with 2 treatment arms
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Treatment arms
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Two different groups will be observed for analysis: (1) Patients receiving CCB monotherapy, ACEi monotherapy, or CCB + ACEi combination therapy
(2) Patients receiving no CCB or ACEi therapy
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Follow-up
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Patients will be assessed every 3 months by history, clinical examination and ECG, and every 6 months by Holter ECG and B-mode echocardiography until the end of the 1-year follow-up
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No randomization (observational trial)
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Justification of recruitment centres/ countries
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The OT will be performed based on the EUSTAR database MEDSonline, which includes approximately 9,600 patients, and the jSScWG taking care of approximately 100 – 120 children and adolescents
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Pre-planned subgroup analyses (effect modification)
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Patients will be subdivided into those (i) without and (ii) with clinically inapparent CB or VA at inclusion as detected by Holter ECG to analyse the treatment effects separately
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Prospective design including patients at risk to develop SHD
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Large sample size
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Feasibility
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Recruiting centers are highly active in the field of SSc clinical research, which guarantees a high quality and accuracy of the collected data
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ClinicalTrials.gov Identifier: |
NCT01829126
For further Information: http://clinicaltrials.gov/ct2/show/NCT01829126?term=desscipher&rank=3 |