A phase III randomized, multi-center, double-blinded, placebo-controlled clinical trial that will examine two strategies for the treatment of acute ischemic stroke associated with a large vessel anterior occlusion within 4.5 hours from symptoms onset: direct endovascular treatment vs. endovascular treatment preceded by intravenous tenecteplase.
Randomized, prospective, multicenter, double-blinded, placebo-controlled clinical trial with adaptive desing. Randomization will be 1:1 according to reperfusion treatment modalities: (A) (with placebo TNK) direct mechanical thrombectomy vs. (B) Intravenous thrombolysis with TNK (0.25 mg/kg) plus mechanical thrombectomy. Randomization will be done by a minimization process using age, National Institute of Health Stroke Scale (NIHSS) score, and site of the occluded artery. For the primary outcome, the subjects will be followed up within 90 days after randomization. The primary outcome will be the ordinal distribution from the modified Rankin scale score (mRS). Subjects presenting acute ischemic stroke within 4.5 hours of the onset of symptoms attributable to an occlusion of intracranial internal carotid or of the proximal middle cerebral artery (MCA, M1- or M2-segment) with or without tandem occlusion of cervical internal carotid confirmed by vascular neuroimaging. Subjects should be eligible for IV thrombolysis. In the sample size calculation, a difference in treatment effect between the groups (achievement of mRS 0 to 2 at 90 days) of 10.6% was considered, with 33.8% in the intervention group (TNK + thrombectomy) and 23.2% in the control group (placebo + thrombectomy), using a unilateral alpha of 0.025, with a power of 80%, resulting in a sample size of 358 participants. Considering a loss ratio of 10%, a sample size of 398 participants is estimated (199 in each treatment arm). An interim analysis is planned to be executed with 50% and 75% of the total sample. It allows the trial to be terminated in the case of efficacy or futility, in addition to enabling adaptive designed based on conditional probability of a positive result.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
Intravenous thrombolysis with tenecteplase 0.25mg/kg
Intravenous administration of placebo, matching the volume of tenecteplase 0.25mg/kg
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, Brazil
RECRUITINGHospital das Clínicas Botucatu
Botucatu, Brazil
RECRUITINGDistribution of the modified Rankin Scale scores at 90 days
Distribution of the modified Rankin Scale scores (shift analysis).
Time frame: 90 days
Functional independence defined as modified Rankin Score ≤ 2
Functional independence defined as modified Rankin Score ≤ 2
Time frame: 90 days
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Infarct volume evaluated on CT at 24 hours (-2/+12 hours).
Time frame: 24 hours
Dramatic early favorable response as determined by a National Institute of Health Stroke Scale (NIHSS) of 0-2 or NIHSS improvement ≥ 10 points at 24 (-2/+12 hours) hours.
Dramatic early favorable response as determined by a National Institute of Health Stroke Scale of 0-2 or NIHSS improvement ≥ 10 points at 24 (-2/+12 hours) hours.
Time frame: 24 hours
Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase
Cost-effectiveness analysis of endovascular therapy alone vs. endovascular therapy associated with tenecteplase
Time frame: 12 months
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year among the groups
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year among the groups
Time frame: 3 months, 6 months and 12 months
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
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QUADRUPLE
Enrollment
398
Hospital de Base do Distrito Federal
Brasília, Brazil
RECRUITINGHospital das Clínicas da UFPR
Curitiba, Brazil
RECRUITINGHospital Geral de Fortaleza
Fortaleza, Brazil
RECRUITINGHospital de Clinicas de Porto Alegre
Porto Alegre, Brazil
RECRUITINGHospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
Ribeirão Preto, Brazil
RECRUITINGHospital de Base de Rio Preto
São José do Rio Preto, Brazil
RECRUITINGHospital das Clínicas de São Paulo
São Paulo, Brazil
RECRUITINGHospital Sao Paulo
São Paulo, Brazil
RECRUITING...and 3 more locations
Score distribution of mRS at 90 days (shift analysis) in patients presenting M2-CMA occlusion
Time frame: 90 days
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Vessel recanalization evaluated by CT angiography or MRA at 24 hours in both treatment groups
Time frame: 24 hours
Vessel recanalization post procedure in the endovascular arm assessed by TIMI grades and adjudicated by a central core-lab. Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 on the post-procedure angiogram.
Vessel recanalization post procedure in the endovascular arm assessed by TIMI grades and adjudicated by a central core-lab. Successful recanalization is defined as TICI (Thrombolysis in Cerebral Infarction) 2b or 3 on the post-procedure angiogram.
Time frame: Immediately Post-procedure