Prospective, multi-center, randomized, controlled, open, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with stentriever and/or Thromboaspiration versus medical management alone. Randomization will be done under a minimization process using age, baseline NIHSS, use of IV tpa, vessel occlusion site and hospital. To evaluate the hypothesis that mechanical thrombectomy is superior to medical management alone in achieving more favorable outcomes in the distribution of the modified Rankin Scale scores at 90 days in subjects presenting with acute large vessel ischemic stroke \<8 hours from symptom onset. Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. Sample size is projected to be 690 patients for a difference in treatment effect of 10%.
Patients with acute ischemic stroke related to anterior circulation large vessel occlusion will be randomized up to 8 hours from symptoms onset in both arms (mechanical thrombectomy versus medical management alone). Subjects are either ineligible for IV alteplase or have received IV alteplase therapy without recanalization. They will be admitted at acute stroke units in Brazil (or ICU if needed) and treated following international guidelines. Concomitant medications and non-pharmacological therapies will be recorded. A maximum of six attempts to retrieve the thrombus in a single vessel can be made. No additional treatment will be allowed either with Intrarterial tPA, mechanical devices or angioplasty/stenting. The primary endpoint will be distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment Interim Analysis The sample size for this Phase III Trial is projected to be 690 subjects. For interim analyses, the method of Lan and DeMets will be used to allocate alpha via the power family method with φ (phi) equal to 1 for the assessment of efficacy and futility, respectively after the first 174, 346 and 518 patients enrolled have completed the 90-day follow-up. The interval may be more frequent if requested by the Data and Safety Monitoring Board (DSMB). At interim analysis, in case the stopping boundaries are crossed the DSMB may recommend stopping the study either for better efficacy of the tested treatment either for futility. Other factors, such as safety, will be taken into consideration by the DSMB in the decision to stop the study. When considering stopping the trial for safety reasons, the DSMB will be instructed to consider both mortality (mRS=6) and severe dependency (mRS=5) at 3 months as one single outcome.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
221
Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever Solitaire FR® and/or thromboaspiration with Penumbra System® versus medical management alone versus medical management alone. A maximum of six attempts to retrieve the thrombus in a single vessel can be made . No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
Patients with acute ischemic stroke with anterior circulation large vessel occlusion will be randomized to receive mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone versus medical management alone. A maximum of six attempts to retrieve the thrombus in a single vessel can be made . No additional treatment will be allowed either with IA tPA, other mechanical devices or angioplasty/stenting.
Hospital Geral de Fortaleza/SUS
Fortaleza, Ceará, Brazil
Hospital Estadual Central
Vitória, Espírito Santo, Brazil
Hospital Geral Roberto Santos
Salvador, Estado de Bahia, Brazil
Hospital de Base do Distrito Federal
Brasília, Federal District, Brazil
Hospital de Clínicas da Universidade Federal do Paraná
Curitiba, Paraná, Brazil
Hospital São José do Avaí
Itaperuna, Rio de Janeiro, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
UNIÃO BRASILEIRA DE EDUCAÇÃO E ASSISTENCIA, Hospital São Lucas PUCRS
Porto Alegre, Rio Grande do Sul, Brazil
Hospital Governador Celso Ramos
Florianópolis, Santa Catarina, Brazil
Clinica Neurologica e Neurocirurgica de Joinville S/S Ltda
Joinville, Santa Catarina, Brazil
...and 5 more locations
Distribution of the modified Rankin Scale scores (shift analysis)
Distribution of the modified Rankin Scale scores at 90 days (shift analysis) as evaluated by two separate assessors who are blinded to treatment
Time frame: 90 days
Functional independence (modified Rankin Score ≤ 2)
Functional independence measured by modified Rankin Score ≤ 2 in 90 days in both groups
Time frame: 90 days
Infarct Burden at 24 hours
ASPECTS change from baseline to 24 hours on CT or MRI
Time frame: 24 hours
Dramatic early favorable response
defined as an NIHSS score 0-2 or a NIHSS score decrease of ≥8 from baseline at 24 hours
Time frame: 24 hours
Cost effectiveness
Cost effectiveness analysis of interventional therapy vs medical therapy alone
Time frame: Life-time horizon perspective
Quality of life analysis
Quality of life analysis as measured by EuroQol/EQ5D at 3 month, 6 months and one year, between interventional therapy vs medical therapy alone
Time frame: 3 months, 6 months, 1 year
Vessel recanalization at 24 hours
Vessel recanalization evaluated by CT angiography (CTA) or MR angiography (MRA) at 24 hours in both treatment groups
Time frame: 24 hours
Successful recanalization at the end of procedure
defined as a grade of 2b or 3 (indicating reperfusion of \>50% of the affected territory) on the modified Thrombolysis in Cerebral Infarction (mTICI) scale
Time frame: immediatelly after procedure (only thrombectomy arm)
Mortality
Mortality at 90 days
Time frame: 90 days
Symptomatic Intracranial hemorrhage
Clinically significant Intracranial hemorrhage (ICH) rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the ECASS criteria for CT evaluation. Symptomatic ICH will be defined as per the SITS-MOST definition: deterioration in NIHSS score of ≥4 points within 24 hours from treatment and evidence of intraparenchymal hemorrhage type 2 in the 22 to 36 hours follow-up imaging scans. The incidence of any asymptomatic hemorrhage measured at 24 (-2/+12) hours will also be compared
Time frame: 24 hours
Procedure related complications
Complications occurring during the procedure will be evaluated: distal embolization in a new territory, arterial dissection, arterial perfuration, groin hematoma
Time frame: During the procedure
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