The SITS-UTMOST: A registry-based prospective study in Europe investigating the impact of regulatory approval of intravenous Actilyse in the extended time window (3-4.5 h) in acute ischaemic stroke

Introduction: The SITS-UTMOST (Safe Implementation of Thrombolysis in Upper Time window Monitoring Study) was a registry-based prospective study of intravenous alteplase used in the extended time window (3-4.5 h) in acute ischaemic stroke to evaluate the impact of the approval of the extended time window on routine clinical practice. Patients and methods: Inclusion of at least 1000 patients treated within 3-4.5 h according to the licensed criteria and actively registered in the SITS-International Stroke Thrombolysis Registry was planned. Prospective data collection started 2 May 2012 and ended 2 November 2014. A historical cohort was identified for 2 years preceding May 2012. Clinical management and outcome were contrasted between patients treated within 3 h versus 3-4.5 h in the prospective cohort and between historical and prospective cohorts for the 3 h time window. Outcomes were functional independency (modified Rankin scale, mRS) 0-2, favourable outcome (mRS 0-1), and death at 3 months and symptomatic intracerebral haemorrhage (SICH) per SITS. Results: 4157 patients from 81 centres in 12 EU countries were entered prospectively (N = 1118 in the 3-4.5 h, N = 3039 in the 0-3 h time window) and 3454 retrospective patients in the 0-3 h time window who met the marketing approval conditions. In the prospective cohort, median arrival to treatment time was longer in the 3-4.5 h than 3 h window (79 vs. 55 min). Within the 3 h time window, treatment delays were shorter for prospective than historical patients (55 vs. 63). There was no significant difference between the 3-4.5 h versus 3 h prospective cohort with regard to percentage of reported SICH (1.6 vs. 1.7), death (11.6 vs. 11.1), functional independency (66 vs. 65) at 3 months or favourable outcome (51 vs. 50). Discussion: Main weakness is the observational design of the study. Conclusion: This study neither identified negative impact on treatment delay, nor on outcome, following extension of the approved time window to 4.5 h for use of alteplase in stroke.