Stroke
Conditions
Keywords
ischemic stroke, tenecteplase, beyond 24 hours
Brief summary
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 intracranial vessel occlusion between 24-72 hours of symptom onset (including wake-up stroke and unwitnessed stroke).
Detailed description
Adult acute ischemic stroke patients due to middle cerebral artery M1-M4 occlusion, ACA, PCA or basilar artery occlusion confirmed by CTA/MRA with baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 or a score of 4 or 5 with a disabling deficit (e.g., hemianopia, aphasia, and loss of hand function) 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 \>1.2, and mismatch volume \>10 mL). 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.
Interventions
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).
DRUGStandard medical treatment
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.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1)Age ≥ 18 years old; * 2)Acute ischemic stroke symptom onset between 24 to 72 hours prior to enrollment; including wake-up stroke and unwitnessed stroke, onset time refers to 'last-seen normal time'; * 3)Pre-stroke modified Rankin scale (mRS) score ≤1; * 4)Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (both inclusive) or a score of 4 or 5 with a disabling deficit (e.g., hemianopia, aphasia, and loss of hand function); * 5)Neuroimaging: 1. Middle cerebral artery M1-M4 occlusion, ACA, PCA or basilar artery occlusion confirmed by CTA/MRA, being responsible for signs and symptoms of acute ischemic stroke; 2. target mismatch profile on CTP or MRI+PWI (ischemic core volume \<70mL, mismatch ratio \>1.2, and mismatch volume \>10mL); * 6)Written informed consent from patients or their legally authorized representatives.
Exclusion criteria
* 1)Present as a significant low-density lesion on CT * 2)Allergy to tenecteplase * 3)Rapidly improving symptoms at the discretion of the investigator * 4)NIHSS consciousness score 1a \>2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate * 5)Persistent blood pressure elevation (systolic ≥185 mmHg or diastolic ≥110 mmHg), despite blood pressure-lowering treatment * 6)Blood glucose \<2.8 or \>22.2 mmol/L (point of care glucose testing is acceptable) * 7)Active internal bleeding or at high risk of bleeding, e.g., major surgery, trauma or gastrointestinal or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days * 8)Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR \>1.7 or prothrombin time \>15 seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of effect can be achieved with a reversal agent; any full dose heparin/heparinoid during the last 24 hours or with an aPTT greater than the upper limit of normal * 9)Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included) * 10)Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation, or giant aneurysm * 11)Any terminal illness such that the patient would not be expected to survive more than 1 year * 12)Unable to perform CTP or PWI * 13)Hypodensity in \>1/3 MCA territory on non-contrast CT for MCA occlusion, and pc-ASPECTS \<6 for BAO * 14)Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI * 15)Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion) * 16)Pregnant women, nursing mothers, or reluctance to use effective contraceptive measures during the period of trial * 17)Unlikely to adhere to the trial protocol or follow-up * 18)Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study * 19)Participation in other interventional clinical trials within the previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| mRS score ≤ 1 at 90 days | 90 days | The proportion of patients with an mRS score ≤ 1 at 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| mRS score | 90 days | Ordinal distribution of mRS at 90 days (shift analysis) |
| mRS score ≤ 2 at 90 days | 90 days | The proportion of patients with an mRS score of 0-2 |
| early neurological improvement at 24h after randomization | 24 hours | The rate of early neurological improvement at 24h after randomization (defined as a NIHSS score ≤1 or ≥4 points compared with baseline) |
| improvement on reperfusion at 24h after randomization (anterior circulation) | 24 hours | The rate of improvement on reperfusion at 24h after randomization (improved by 90% on Tmax \> 6s) for stroke with anterior circulation occlusions |
| complete recanalization at 24h after randomization | 24 hours | The rate of complete recanalization at 24h after randomization (defined as an AOL score of 3) |
| Symptomatic intracranial hemorrhage within 36 hours | 36 hours | Symptomatic intracranial hemorrhage within 36 hours (defined by the ECASS III criteria) |
| All-cause mortality at 90 days | 90 days | All-cause mortality at 90 days |
| Systemic bleeding at 90 days | 90 days | Systemic bleeding at 90 days (defined by the GUSTO criteria: moderate and severe bleeding) |
Countries
China
Contacts
CONTACTYongjun Wang
Outcome results
None listed