TY - JOUR T1 - A randomised, open-label trial to assess the optimal treatment strategy in early diffuse cutaneous systemic sclerosis: the UPSIDE study protocol JF - BMJ Open JO - BMJ Open DO - 10.1136/bmjopen-2020-044483 VL - 11 IS - 3 SP - e044483 AU - Julia Spierings AU - Anna van Rhenen AU - Paco MW Welsing AU - Anne CA Marijnissen AU - Ellen De Langhe AU - Nicoletta Del Papa AU - Daan Dierickx AU - Karina R Gheorghe AU - Joerg Henes AU - Roger Hesselstrand AU - Tessa Kerre AU - Per Ljungman AU - Arjan A van de Loosdrecht AU - Erik WAF Marijt AU - Miro Mayer AU - Marc Schmalzing AU - Roland Schroers AU - Vanessa Smith AU - Reinhard E Voll AU - Madelon C Vonk AU - Alexandre E Voskuyl AU - Jeska K de Vries-Bouwstra AU - Ulrich A Walker AU - Dirk M Wuttge AU - Jacob M van Laar Y1 - 2021/03/01 UR - http://bmjopen.bmj.com/content/11/3/e044483.abstract N2 - Introduction Systemic sclerosis (SSc) is a chronic, autoimmune connective tissue disease associated with high morbidity and mortality, especially in diffuse cutaneous SSc (dcSSc). Currently, there are several treatments available in early dcSSc that aim to change the disease course, including immunosuppressive agents and autologous haematopoietic stem cell transplantation (HSCT). HSCT has been adopted in international guidelines and is offered in current clinical care. However, optimal timing and patient selection for HSCT are still unclear. In particular, it is unclear whether HSCT should be positioned as upfront therapy or rescue treatment for patients refractory to immunosuppressive therapy. We hypothesise that upfront HSCT is superior and results in lower toxicity and lower long-term medical costs. Therefore, we propose this randomised trial aiming to determine the optimal treatment strategy for early dcSSc by comparing two strategies used in standard care: (1) upfront autologous HSCT versus (2) immunosuppressive therapy (intravenous cyclophosphamide pulse therapy followed by mycophenolate mofetil) with rescue HSCT in case of treatment failure.Methods and analysis The UPSIDE (UPfront autologous hematopoietic Stem cell transplantation vs Immunosuppressive medication in early DiffusE cutaneous systemic sclerosis) study is a multicentre, randomised, open-label, controlled trial. In total, 120 patients with early dcSSc will be randomised. The primary outcome is event-free survival at 2 years after randomisation. Secondary outcomes include serious adverse events, functional status and health-related quality of life. We will also evaluate changes in nailfold capillaroscopy pattern, pulmonary function, cardiac MR and high-resolution CT of the chest. Follow-up visits will be scheduled 3-monthly for 2 years and annually in the following 3 years.Ethics and dissemination The study was approved by the Dutch Central Committee on Research Concerning Human Subjects (NL72607.041.20). The results will be disseminated through patient associations and conventional scientific channels.Trial registration numbers NCT04464434; NL 8720. ER -