Effects of human urinary kallidinogenase on early neurological improvement and functional outcomes in acute ischaemic stroke (TK-SPEED): protocol for a multi-centre, randomised, open-label, blinded-endpoint controlled study.

BACKGROUND: A considerable number of patients with acute ischaemic stroke (AIS) are ineligible for standard reperfusion therapy due to time window constraints and contraindications. Human urinary kallidinogenase (HUK), a tissue kallikrein, has been demonstrated to promote vasodilation and improve cerebral blood flow (CBF) in ischaemic regions. Although clinical evidence suggests its favourable efficacy in such patients with AIS, the specific effects of HUK on early cerebral perfusion and its correlation with functional outcomes remain incompletely elucidated. AIM: TK-SPEED aims to investigate the effects of HUK on early cerebral perfusion improvement and functional outcomes in patients with AIS, providing robust evidence for HUK. METHODS AND DESIGN: TK-SPEED is a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Approximately 540 participants with acute anterior circulation ischaemic stroke will be recruited from about 20 participating sites across China. Eligible patients will be randomly assigned in a 1:1 ratio to either the intervention group (HUK plus standard therapy) or the control group (standard therapy). STUDY OUTCOMES: The primary endpoint is the proportion of patients with a modified Rankin Scale (mRS) of 0-2 at day 90. The secondary outcomes include changes in the Tmax (time-to-maximum)>6 s volume and regional CBF in the Tmax>6 s area on CT perfusion from baseline to day 5 after treatment, the ordinal distribution of mRS, the proportion of patients with mRS of 0-1 at day 90 and changes in the National Institutes of Health Stroke Scale score from baseline to days 5 and 10 after treatment. DISCUSSION: This trial will provide crucial evidence elucidating the impact of HUK on early cerebral perfusion and its correlation with the 90-day neurological outcomes in patients with AIS, offering guidance for optimising AIS treatment strategies and improving patient prognosis. TRIAL REGISTRATION NUMBER: NCT06132880.