Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE): A multicentre, prospective, randomised, open-label, blinded endpoint, controlled phase III non-inferiority trial protocol.

Abstract

RATIONALE: Alteplase is the only approved thrombolytic agent for acute stroke. An alternative plasminogen activator, tenecteplase, has been previously shown to increase early biological effectiveness (reperfusion) resulting in early clinical recovery in acute stroke patients with target mismatch on perfusion imaging, however phase III data is lacking.Aim and hypothesis: In this study, we assess the efficacy and safety of tenecteplase compared to alteplase in acute stroke patients with target mismatch on perfusion imaging. METHODS AND DESIGN: The tenecteplase (0.25mg/kg) versus alteplase (0.9mg/kg) for Stroke Thrombolysis Evaluation (TASTE) is a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled phase III non-inferiority trial (2 arms with 1:1 randomisation) with an adaptive sample size re-estimation, in patients with acute ischaemic stroke, meeting target mismatch criteria on brain perfusion imaging.Sample size estimates: Recruiting 728 patients (1:1 tenecteplase vs alteplase) would yield 90% power (two-sided alpha 0.05) to detect a treatment effect of 8% (26% mRS 0-1 in alteplase arm and 34% mRS 0-1 in tenecteplase arm), with an absolute non-inferiority margin of 3%. Following the pre-planned "promising zone" adaptive sample size re-estimation with the maximum sample size capped at 1024 patients, the final sample size was set at 832 patients. STUDY OUTCOMES: The primary outcome measure is the proportion of patients with a modified Rankin Scale (mRS) score of 0-1 at 3-months. Secondary outcomes include the categorical shift in mRS at 3-months, the proportion of patients with mRS 0-2,5-6 and 6; reduction of the National Institutes of Health Stroke Scale (NIHSS) by 8 or more points or reaching 0-1 at 24-hours; symptomatic intracerebral haemorrhage within 36-hours; and death. DISCUSSION: This pivotal trial will provide important data on the role of tenecteplase in acute ischemic stroke, and the use of imaging-based treatment decision making for stroke thrombolysis.