Ten years of interventional research in systemic sclerosis: a systematic mapping of trial registries

OBJECTIVE: To provide a comprehensive overview of interventional clinical trials registered in international databases and planned and conducted within the last 10 years in patients with systemic sclerosis (SSc). METHODS: We searched the International Clinical Trials Registry Platform for all records on interventional clinical trials targeting patients with SSc performed since September 2007. Two reviewers selected studies according to the prespecified eligibility criteria. Information on start date, country of origin, funding sources, phase of development, study design, (planned) sample size, enrollment status, outcomes, disease complication, and treatments investigated were retrieved and summarized. RESULTS: Among the 198 eligible studies identified (122 randomized controlled trials [RCTs; 62%]), 87 (30%) were conducted in Europe, 165 (83%) in a single country, and 81 (41%) were industry-funded. The majority of trials investigated pharmacologic treatments (75%), mostly nonbiotherapies (57%). RCTs were mostly 2-arm (82%) placebo-controlled (71%) studies with a median number of patients enrolled or planned to be enrolled of 40 (interquartile range 25-77 [range 10-586]). Twenty-one RCTs (17%) planned to enroll or enrolled >100 patients. Time to assess the primary outcome was found to be adequate in 29% to 50% of RCTs retrieved. Patients age >65 years were excluded in 14% of studies. SSc complications more frequently investigated in overall studies were skin thickness (26%), Raynaud's phenomenon/digital ulcers (24%), and interstitial lung disease (14%). CONCLUSION: The SSc research landscape is dominated by small, short, and mainly placebo-controlled trials, especially investigating pharmacologic treatments. Some patients' needs continue to be neglected.