SPREAD-STACI study: A protocol for a randomized multicenter clinical trial comparing urgent with delayed endarterectomy in symptomatic carotid artery stenosis Gaetano Lanza 1 *, Stefano Ricci 2 , Francesco Speziale 3 , Danilo Toni 4 , Enrico Sbarigia 3 , Carlo Setacci 5 , Carlo Pratesi 6 , Francesco Somalvico 7 , Augusto Zaninelli 8 , and Gian Franco Gensini 9 Rationale In patients with >50% carotid artery stenosis (as measured by North American Symptomatic Carotid Endarter- ectomy Trial (NASCET) criteria) suffering a transient ischemic attack or a minor ipsilateral stroke, carotid endarterectomy exerts maximum benefits, when performed within the first 15 days from the initial ischemic symptom. It is also known that the probability of a major stroke spikes within the first few days after a transient ischemic attack/minor stroke and then flattens out in the following days and weeks. It could be hypothesized that urgent carotid endarterectomy has greater benefit than delayed procedure. Aims Demonstrate that urgent carotid endarterectomy is more effective than delayed interventions. Design Centers employing neurolgist/stroke physicians and vascular surgeons will enroll TIA or minor stroke patients with >50 % carotid artery stenosis (Nascet criteria), rand- omized in two groups: 1) urgent carotid endarterectomy (within 48 hours) and 2) delayed carotid endarterectomy ( operated between 48 hours and 15 days after onset of symptoms) Risk factors will be evaluated at enrollment. TIA will be classified by ABCD2 scoring system,and minor stroke by National Institutes of Health Stroke Scale (NIHSS) scores. The study will last 90 days per patient,starting from their initial symptom,and the follow-up will be performed by an indipendent neurologist. A total of 456 patients (228 / group) is needed to observe an absolute difference of 10% between groups. Outcomes Primary end-point is reduction in all types of stroke, AMI or death in urgent endarterectomy groupo com- pared to delayed ones. Secondary end-points are: – Reduction of ipsilateral ischemic stroke in group 1 with respect to Group 2 – Identification of predictive risk factors and – Confirmation of no different rate for hemorragic/ ischemiccomplications between groups. Key words: randomized clinical trial, stroke prevention, symptomatic carotid stenosis, urgent vs. delayed carotid endarterectomy Introduction The two main surgical trials on carotid artery stenosis con- ducted in the 1980s – North American Symptomatic Carotid Endarterectomy Trial (NASCET) (1) and European Carotid Surgery Trial (ECST) (2) – demonstrated the net benefit afforded by carotid endarterectomy (CEA), with respect to medical therapy alone, in patients with >50% carotid stenosis (as measured by the NASCET criteria) that had been sympto- matic for minor stroke, transient ischemic attacks (TIA), or amaurosis fugax in the previous six-months. The benefit was discernible as a reduction in the five-year risk of recurring stroke and death. Recent revision of NASCET and ECST datasets demon- strated that the benefit of CEA is superior (Number Needed to Treat or NNT,5) in patients operated on within the first two- weeks from the initial ischemic event than in patients having undergone surgery after >12 weeks from the initial ischemic event (NNT, 125): in other words, CEA is more effective the earlier it is performed (3). Correspondence: Gaetano Lanza*, Vascular Surgery Department, IRCCS MultiMedica Hospital, Viale Piemonte, 70, 21053 Castellanza, Italy. Email: gaetano.lanza@multimedica.it 1 Vascular Surgery Department, IRCCS MultiMedica Hospital, Castellanza, Italy 2 Department of Neurology, ASL 1 Citta’ di Castello and Branca, Italy 3 Vascular Surgery Department, Policlinico Umberto I, ‘La Sapienza’ University, Rome, Italy 4 Emergency Department Stroke Unit, Policlinico Umberto I, La Sapienza University Rome, Italy 5 Vascular Endovascular Surgery Unit, Department of Surgery, University of Siena, Italy 6 Vascular Surgery Unit, University of Florence, Italy 7 Biostatistics Service, IRCCS Multimedica Hospital, Sesto San Giovanni, Italy 8 School of Medicine, University of Florence, Italy 9 Department of Critical Care, University of Florence, Italy Conflicts of Interest: None declared. DOI: 10.1111/j.1747-4949.2011.00699.x Protocols © 2011 The Authors. International Journal of Stroke © 2011 World Stroke Organization Vol 7, January 2012, 81–85 81