Cardiovascular Events And
Mortality In Systemic Sclerosis: A Study Of The Effect Of Iloprost
On These And On Disease Progression:– The “SSTEP” Study
Study Sponsor:
University of Dundee, The
Raynaud's & Scleroderma Association. UK.
Coordinating center: Professor
JJF Belch, University Division of Medicine, Ninewells Hospital,
DUNDEE. United Kingdom
Other centers: Professor George Nuki & Dr Euan McRorie,
University Department of Rheumatology, Royal Infirmary, EDINBURGH.
UK Dr Rajan Madhok, Centre for Rheumatic Diseases, Royal Infirmary,
GLASGOW. UK Dr Clifford Eastmond, Dr Hazem Youssef, Department of
Rheumatology Aberdeen Royal Infirmary, ABERDEEN Professor Douglas
Veale, Department of Rheumatology, St Vincent’s Hospital, DUBLIN.
Ireland. Professor Paul Emery, Department of Rheumatology, Leeds
General Infirmary, LEEDS. UK Dr Meilien Ho, Department of
Rheumatology, Northampton General Hospital, NORTHAMPTON. UK Dr
Bridget Griffiths, Department of Rheumatology, The Freeman Hospital,
NEWCASTLE. UK Professor Chris Denton, Dept of Rhuematology, Royal
Free Hospital, LONDON.
Design: Multi centre, Double blind,randomised placebo
controlled trial.
Inclusion criteria: a) any patient fulfilling ARC criteria
for SSc; b) any patient with Raynaud’s Phenomenon and at least 3
other features of limited SSc; or c) any patient with Raynaud’s
Phenomenon and the presence of an SSc-related autoantibody (eg
anticentromere, antitopo1 [scleroderma 70], anti-U1RNP, anti-ThRNP,
anti-U3RNP, anti-PmScl). All >40 years of age.
Exclusion criteria: suspected serious physical illness such
as cancer which may be expected to curtail life expectancy,
psychiatric illness (reported by GP) and congenital heart disease.
Exclusion will also be made of any patient who is pregnant or who
wishes to become pregnant within the time course of the study.
Primary outcome measure: A composite primary endpoint is
sought for this study. 1) Fatal Coronary and stroke events plus non
fatal myocardial infarction and stroke, 2) Vascular disease death,
and 3) SSc disease progression to include a) deteriorating renal
function as measured by 24-hour urine and blood sampling for
creatinine clearance, b) deteriorating lung function as measured by
changes in DLCO total lung capacity, c) increase in pulmonary artery
pressure measured in millimetres in mercury by echocardiogram and d)
skin score assessed using the modified Rodnan Skin Score. (These
will be monitored and percentage change from baseline calculated. If
deterioration is indicated by an increasing figure then 30% change
will be required. If deterioration is based on a decreasing number
then 20% change from baseline will be required. Additionally the
Medsger categories will be evaluated. The definition of the above CV
events will be made according to the WHO Criteria for the diagnosis
of coronary events and stroke (fatal and non-fatal).
Secondary outcome measures: main secondary endpoints are 1)
All cause mortality, 2) Non-fatal myocardial infarction and stroke,
3) Occurrence of other vascular events including requirement of
coronary or peripheral arterial bypass surgery and/or angioplasty,
development of angina, claudication or development of critical limb
ischaemia, and 4) Severity of Raynaud’s Phenomenon.
Recruitment period: Feb 2002 to Feb 2005
Completion: 31st Dec 2008
Date of expected analysis: Sept 2009