Tenecteplase Reperfusion therapy in Acute ischaemic Cerebrovascular Events-II (TRACE II): rationale and design

BACKGROUND AND PURPOSE: Tenecteplase (TNK) is a promising agent for treatment of acute ischaemic stroke (AIS). We hypothesised that recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) is non-inferior to rt-PA in achieving excellent functional outcome at 90 days, when administered within 4.5 hours of ischaemic stroke onset. METHODS AND DESIGN: Tenecteplase Reperfusion therapy in Acute ischemic Cerebrovascular Events (TRACE) is a phase III, multicentre, prospective, randomised, open-label, blinded-end point non-inferiority study. Patients eligible for intravenous thrombolysis therapy are randomised to rhTNK-tPA 0.25 mg/kg (single bolus) to a maximum of 25 mg or rt-PA 0.9 mg/kg (10% bolus+90% infusion/1 hour) to a maximum of 90 mg. Medications considered necessary for the patient’s health may be given at the discretion of the investigator during 90-day follow-up. STUDY OUTCOMES: The primary study outcome is excellent functional outcome defined as modified Rankin Scale (mRS) 0–1 at 90 days. Secondary efficacy outcomes include favourable functional outcome defined as mRS ≤2 at 90 days, ordinal distribution of mRS and major neurological improvement on the National Institutes of Health Stroke Scale. Safety outcomes are symptomatic intracranial haemorrhage within 36 hours and death from any cause. DISCUSSION: There is no completed registration study of TNK in AIS worldwide. TRACE II strives to provide evidence for a new drug application for rhTNK-tPA in AIS within 4.5 hours through a well-designed and rigorously executed randomised trial in China. TRIAL REGISTRATION NUMBER: NCT04797013.