Stroke, Ischemic
Conditions
Keywords
stroke, ischemic stroke, thrombectomy, treatment, acute stroke
Brief summary
A phase III, randomized, multi-center, open label clinical trial that will examine whether endovascular treatment is superior to standard medical therapy alone in patients who suffer a large vessel anterior circulation ischemic stroke within 8-24 hours from time last seen well
Detailed description
Prospective, multi-center, randomized, controlled, open-label, blinded-endpoint trial with a sequential design. The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone in patients who suffer a large vessel anterior circulation ischemic stroke between 8 and 24 hours from time last seen well. Randomization will be done under a minimization process using age (≤68 vs. \>68 years), baseline NIHSS (\<17 v. ≥17), ASPECTS (5-7 vs. 8-10), therapeutic window (6-12 or 12-24 hours after TLKW), occlusion site (Intracranial ICA or M1), and clinical site. For the primary endpoint, subjects will be followed for 90 days post-randomization. Sham endovascular procedure has been rejected due to the medical risk of the angiography and practical issues that difficult to maintain blindness of investigators.
Interventions
DEVICEThrombectomy
Endovascular treatment of large vessel occlusion (mechanical thrombectomy) with stent-retriever and/or thromboaspiration (neurointerventionalist choice)
Sponsors
Hospital das Clínicas de Ribeirão Preto
Hospital Geral de Fortaleza
Hospital de Base
Federal University of São Paulo
Fundação Faculdade Regional de Medicina de São José do Rio Preto
UPECLIN HC FM Botucatu Unesp
University of Campinas, Brazil
Irmandade Santa Casa de Misericórdia de Porto Alegre
Universidade Federal do Paraná
Hospital Estadual Central
Hospital Sao Jose do Avai
Irmandade da Santa Casa de Misericordia de Sao Paulo
Federal University of Uberlandia
Instituto de Assistencia Medica ao Servidor Publico Estadual, Sao Paulo
Hospital de Clinicas de Porto Alegre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Sham endovascular procedure has been rejected due to the medical risk of the angiography and practical issues that difficult to maintain blindness of investigators. For the primary endpoint, subjects will be followed for 90 days post-randomization. Distribution of the modified Rankin Scale scores at 90 days will be evaluated by two separate assessors who are blinded to treatment. Primary Endpoint will consider central core lab readings only (video interview with RFA method) with local reading as a back-up mechanism.
Intervention model description
The randomization employs a 1:1 ratio of mechanical thrombectomy with stent-retriever and/or thromboaspiration versus medical management alone
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment or the treatment is contraindicated (e.g., subject presents beyond recommended time from symptom onset), or where patient has received IV thrombolytic therapy without clinical improvement. 2. No significant pre-stroke functional disability (mRS ≤2) 3. Baseline NIHSS score obtained prior to randomization must be equal or higher than 8 points (assessed within one hour prior to qualifying imaging) 4. Age ≥18 years (no upper age limit) 5. Occlusion (TICI 0-1) of the intracranial ICA (distal ICA or T occlusions) and/or MCA-M1 segment suitable for endovascular treatment, as evidenced by CTA, MRA or angiogram, with or without concomitant cervical carotid occlusion or stenosis. 6. The presence of Age-Adjusted modified Clinical ASPECTS Mismatch (mCAM) defined as ASPECTS 5-10 and one of the following criteria: 1. NIHSS ≥ 8 and \>50% involvement in 0-1 Cortical (e.g. M1-6) ASPECTS areas (any age); 2. NIHSS ≥ 8 and \>50% involvement in 0-2 Cortical (e.g. M1-6) ASPECTS areas (and age \< 80 years old); 3. NIHSS ≥ 15 and \>50% involvement in 0-3 Cortical (e.g. M1-6) ASPECTS areas (and age \< 80 years old). 7. Patient treatable within 6-24 hours of symptom onset. Symptoms onset is defined as point in time the patient was last seen well (at baseline). Treatment start is defined as arterial puncture. 8. Informed consent obtained from patient or acceptable patient surrogate
Exclusion criteria
-Clinical criteria 1. Known hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR \> 3.0 2. Baseline platelet count \< 30.000/µL 3. Baseline blood glucose of \< 50mg/dL 4. Severe, sustained hypertension (SBP \> 185 mm Hg or DBP \> 110 mm Hg) NOTE: If the blood pressure can be successfully reduced and maintained at the acceptable level using AHA guidelines recommended medication (including iv antihypertensive drips), the patient can be enrolled. 5. Patients in coma defined as totally unresponsive; responding only with reflexes or being areflexic (Intubated patients for transfer could be randomized only in case an NIHSS is obtained by a neurologist prior transportation). 6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS 7. Serious, advanced, or terminal illness with anticipated life expectancy of less than one year. 8. History of life-threatening allergy (more than rash) to contrast medium 9. Subjects who has received IV t-PA treatment beyond 4.5 hours from the beginning of the symptoms 10. Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission. 11. Subject participating in a study involving an investigational drug or device that would impact this study. 12. Cerebral vasculitis 13. Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations, mRS score at baseline must be ≤2. This excludes patients who are severely demented, require constant assistance in a nursing home type setting or who live at home but are not fully independent in activities of daily living (toileting, dressing, eating, cooking and preparing meals, etc.) 14. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas). \- Neuroimaging criteria 15. Hypodensity on CT or restricted diffusion on MRI amounting to an ASPECTS score of \<5. 16. Complete involvement of more than 3 cortical ASPECTS areas (e.g. M1, M2, M3, M4, M5, or M6). 17. Complete absence of leptomeningeal collaterals on CT angiography (e.g. Malignant CTA pattern or score 0). 18. CT or MR evidence of hemorrhage (the presence of GRE microbleeds is allowed). 19. Significant mass effect with midline shift. 20. Evidence of ipsilateral carotid occlusion, high grade stenosis or arterial dissection in the extracranial or petrous segment of the internal carotid artery that cannot be treated or will prevent access to the intracranial clot or excessive tortuosity of cervical vessels precluding device delivery/deployment 21. Subjects with occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation) 22. Evidence of intracranial tumor (except small meningioma).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin Scale scores | 90 days | Distribution of the modified Rankin Scale scores at 90 days (shift analysis). The score range from zero to 6 with higher values indicating a worst functional outcome at 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disability on the utility-weighted modified Rankin scale (UW-mRS) | 90 days | Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS). The score range from 1 to zero with higher values indicating a better functional outcome at 90 days |
| Quality of life measured by EuroQol Group 5-Dimension Self-Report Questionnaire (EuroQol / EQ5D) | 90 days and 1 year | Quality of life analysis as measured by EuroQol/EQ5D 5-Dimension Self-Report Questionnaire, on which scores range from -0.176 to 1, with higher values indicating a better quality of life\]) at 90 days |
| Proportion of Patients with Functional independence in 90 days | 90 days | Functional independence defined as mRS ≤2 |
| Proportion of patients with Intracranial Hemorrhage at 24 hours | 24 hours | Clinically significant ICH rates at 24 (-2/+12) hours. All intracerebral hemorrhages will be classified by a central core-lab using the Heidelberg criteria. 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. |
| Procedural related complications | immediately after procedure | Procedural related complications: arterial perforation, arterial dissection, and embolization in a previously uninvolved vascular territory |
| Mortality at 90 days | 90 days | Mortality at 90 days |
Countries
Brazil
Contacts
Primary ContactSheila CO Martins, MD, PhD
Backup ContactNatacha Fleck
Outcome results
None listed