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| Name | Class |
|---|---|
| Ministry of Health, Brazil | OTHER_GOV |
| Medtronic | INDUSTRY |
| Penumbra Inc. | INDUSTRY |
| iSchemaView, Inc |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| thrombectomy | Experimental | mechanical thrombectomy with stentriever Solitaire FR® and/or thromboaspiration with Penumbra System® in patients with large vessel occlusion in cerebral anterior circulation vessels |
|
| best medical treatment | No Intervention | best medical treatment in patients with acute ischemic stroke with anterior circulation large vessel occlusion |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Thrombectomy | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| Functional independence (modified Rankin Score ≤ 2) | Functional independence measured by modified Rankin Score ≤ 2 in 90 days in both groups | 90 days |
| Infarct Burden at 24 hours | ASPECTS change from baseline to 24 hours on CT or MRI |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raul Nogueira, MD | Emory University | Principal Investigator |
| Sheila CO Martins, MD | Hospital de Clínicas de Porto Alegre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Geral de Fortaleza/SUS | Fortaleza | Ceará | Brazil | |||
| Hospital Estadual Central |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38182456 | Derived | Silva GS, Alves MM, Barros FCD, Frudit ME, Pontes-Neto OM, Mont'Alverne FJ, Rebello LC, Carbonera LA, Abud DG, Lima F, de Souza AC, Liebeskind D, Mosmann G, Bezerra D, Saver J, Cardoso F, Nogueira RG, Martins SO. The role of intravenous thrombolysis before mechanical Thrombectomy: A subgroup analysis of the RESILIENT trial. J Neurol Sci. 2024 Feb 15;457:122853. doi: 10.1016/j.jns.2023.122853. Epub 2023 Dec 20. | |
| 32521133 |
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| UNKNOWN |
| Brainomix Limited | INDUSTRY |
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|
| Stentriever Solitaire FR® or Penumbra System® | Device | 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. |
|
| 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 | 24 hours |
| Cost effectiveness | Cost effectiveness analysis of interventional therapy vs medical therapy alone | 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 | 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 | 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 | immediatelly after procedure (only thrombectomy arm) |
| Mortality | Mortality at 90 days | 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 | 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 | During the procedure |
| 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 | 90035903 | 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 |
| Hospital das Clínicas da Faculdade de Medicina de Botucatu | Botucatu | São Paulo | Brazil |
| Hospital de Clínicas - UNICAMP | Campinas | São Paulo | Brazil |
| Hospital de Clínicas de Ribeirão Preto | Ribeirão Preto | São Paulo | Brazil |
| Irmandade da Santa Casa de Misericórdia | São Paulo | São Paulo | Brazil |
| Universidade Federal de São Paulo - UNIFESP/EPM | São Paulo | Brazil |
| Derived |
| Martins SO, Mont'Alverne F, Rebello LC, Abud DG, Silva GS, Lima FO, Parente BSM, Nakiri GS, Faria MB, Frudit ME, de Carvalho JJF, Waihrich E, Fiorot JA Jr, Cardoso FB, Hidalgo RCT, Zetola VF, Carvalho FM, de Souza AC, Dias FA, Bandeira D, Miranda Alves M, Wagner MB, Carbonera LA, Oliveira-Filho J, Bezerra DC, Liebeskind DS, Broderick J, Molina CA, Fogolin Passos JE, Saver JL, Pontes-Neto OM, Nogueira RG; RESILIENT Investigators. Thrombectomy for Stroke in the Public Health Care System of Brazil. N Engl J Med. 2020 Jun 11;382(24):2316-2326. doi: 10.1056/NEJMoa2000120. |
| 30758449 | Derived | Gagliardi VDB, Gagliardi RJ. Current and future conditions of stroke care in Brazil. Arq Neuropsiquiatr. 2019 Jan;77(1):68-69. doi: 10.1590/0004-282X20180160. No abstract available. |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D017131 | Thrombectomy |
| ID | Term |
|---|---|
| D014656 | Vascular Surgical Procedures |
| D013504 | Cardiovascular Surgical Procedures |
| D013514 | Surgical Procedures, Operative |
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