The benefit-risk profile of thrombolysis for acute ischemic strokes beyond 24 hours has never been investigated. We initiated a multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled trial to assess the safety and efficacy of tenecteplase (0.25mg/kg, max 25mg) versus standard medical treatment in acute ischemic stroke due to large vessel occlusion between 24-72 hours of symptom onset (including wake-up stroke and unwitnessed stroke).
Adult acute ischemic stroke patients due to large vessel occlusion (Middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA) with baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 will be enrolled in this trial. We use perfusion imaging to select subjects and the enrolled patients have target mismatch profile on CTP or MRI+PWI (ischemic core volume \<70mL, mismatch ratio ≥1.8, and mismatch volume ≥15mL). We will randomly assign patients who have salvageable brain tissue as identified on perfusion imaging to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 24 to 72 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome is the proportion of patients with an mRS score ≤ 1 at 90 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
330
Each vial of tenecteplase is reconstituted with 3 ml sterile water for injection and adjusted to a concentration of 5.33 mg/ml. Calculate the total amount of drug according to the subject's actual body weight and measure the required drug volume. The maximum dose should not exceed 25mg. Tenecteplase should be given as a single, intravenous bolus (within 5-10 seconds).
Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone after randomization at the discretion of site researchers according to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.
Beijing tiantan hospital
Beijing, China
RECRUITINGmRS score ≤ 1 at 90 days
The proportion of patients with an mRS score ≤ 1 at 90 days
Time frame: 90 days
mRS score
Ordinal distribution of mRS at 90 days (shift analysis)
Time frame: 90 days
mRS score ≤ 2 at 90 days
The proportion of patients with an mRS score of 0-2
Time frame: 90 days
early neurological improvement at 24h after randomization
The rate of early neurological improvement at 24h after randomization (defined as a NIHSS score ≤1 or ≥4 points compared with baseline)
Time frame: 24 hours
improvement on reperfusion at 24h after randomization
The rate of improvement on reperfusion at 24h after randomization (improved by 90% on Tmax \> 6s)
Time frame: 24 hours
complete recanalization at 24h after randomization
The rate of complete recanalization at 24h after randomization (defined as an AOL score of 3)
Time frame: 24 hours
Symptomatic intracranial hemorrhage within 36 hours
Symptomatic intracranial hemorrhage within 36 hours (defined by the ECASS III criteria)
Time frame: 36 hours
All-cause mortality at 90 days
All-cause mortality at 90 days
Time frame: 90 days
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Systemic bleeding at 90 days
Systemic bleeding at 90 days (defined by the GUSTO criteria: moderate and severe bleeding)
Time frame: 90 days