SITS (Safe Implementation of Treatments in Stroke) Open Artery by Thrombectomy in Acute Occlusive Stroke Study

Study Overview
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Brief Summary
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Ischemic stroke, i.e. irreversible damage of a part of the patient's brain, is caused by the formation of blood clot in the major vessel which gives blood supply to a certain part of the brain. At early time, within the first 4,5 hours, the conventional treatment is to try to dissolve this blood clot with a medication (thrombolytic drug) which is administered to the blood through the needle in the vein. If the clot still remains there, additional treatment is possible - going directly to the clot via artery and taking it out with a special device. Patients may be included even if they are not treated with intravenous thrombolysis because of contraindication or other reasons. The purpose of the present study is to evaluate the benefit and safety efficacy of thrombectomy and standard stroke care in clinical routine treatment of acute occlusive stroke compared to standard stroke care only.

Official Title
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An Open, Prospective, Blinded Evaluation, International, Multicentre, Controlled Study of Safety and Efficacy of Thrombectomy and Standard Stroke Care in Clinical Routine Treatment of Acute Occlusive Stroke Compared to Standard Stroke Care Only

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Device: Stent retriever endovascular device for thrombectomy
* Drug: Intravenous thrombolysis by alteplase (Actilyse) (optional)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients with acute stroke after exclusion of intracranial haemorrhage on CT/MRI scan. Confirmed diagnosis on CTA of persisting occlusion of the terminal Internal Carotid Artery (Car-T), proximal Middle Cerebral Artery (MCA, M1), proximal part of the insular segment of MCA (M2), proximal part of the anterior cerebral artery (A1), Basilar Artery (BA) or proximal part of the posterior cerebral artery (P1), consistent with the clinical symptoms. For inclusion in the study, CTA must not be performed later than 15 minutes after IVT start if given. For patients not treated with IVT, CTA should preferably be performed within 15 minutes of completion of the non-contrast CT but must be performed within 6 hours after stroke onset. Eligible patients for IVT are treated according to clinical guidelines (Attachment 1), and IVT, if given, initiated within 4.5 h. Initiation of thrombectomy is recommended within 6 hours after stroke onset but must be performed within to 8 hours if thrombectomy would still be of benefit for the patient as judged by the investigator. Baseline NIHSS Score at initiation of IVT is recommended between 7 and 25 for anterior circulation stroke and ≥7 without upper limit for posterior circulation stroke (baseline NIHSS score should be assessed by an NIHSS-certified physician), but patients may also be included beyond these scores if thrombectomy would still be of benefit for the patient as judged by the investigator. Age ≥18years. Anticipated life expectancy of at least 6 months. Patient or legal representative is competent to make a decision and has provided informed consent with regard to participation in the study, retrieval and storage of data and follow up procedures. Initiation of endovascular procedure (DSA/TBY, defined as start with groin puncture) within 2 hours from the start of IVT, or after CTA if IVT is not given (for TBY arm patients). Exclusion criteria: Known significant pre-stroke disability (mRS ≥2). Extended early ischemic changes for basilar artery occlusion, according to the judgment of treating physician based on routine clinical practice of the hospital; if technical possibility exists, early irreversible ischemic changes may be confirmed by pc-ASPECTS score < 8 on CTASI (2) or extensive DWI lesion on pre-treatment MRI. Known pregnancy. Participation in any other investigational drug or device study, currently or in the previous 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombectomy<br>Thrombectomy arm consists of patients undergoing thrombectomy according to accepted critera in the judgement of investigator. Patients may be included even if they are not treated with intravenous thrombolysis because of contraindication or other reasons. | Device: Stent retriever endovascular device for thrombectomy<br>* Thrombectomy by selected stent retrievers (TREVO, Solitaire, pREset, in special cases all stent retrievers) as additional therapy in major artery occlusion in patients fulfilling criteria for and receiving intravenous thrombolysis<br>* Other names: Mechanical thrombectomy in ischemic stroke;Drug: Intravenous thrombolysis by alteplase (Actilyse) (optional)<br>* Stroke thrombolysis with Alteplase (Boeringer-Ingelheim, ATC-code B01AD02; a fibrinolytic drug) according to conventional guidelines (0.9 mg/kg, not exceeding 90 mg, given intravenously)<br>* Other names: Stroke thrombolysis;|
| Active Comparator: Control<br>Control arm patients are treated with standard stroke care including IVT but do not receive Thrombectomy. Control arm consists of patients fulfilling criteria for thrombectomy according to accepted critera in the judgement of investigator. Patients may be included even if they are not treated with intravenous thrombolysis because of contraindication or other reason. | Drug: Intravenous thrombolysis by alteplase (Actilyse) (optional)<br>* Stroke thrombolysis with Alteplase (Boeringer-Ingelheim, ATC-code B01AD02; a fibrinolytic drug) according to conventional guidelines (0.9 mg/kg, not exceeding 90 mg, given intravenously)<br>* Other names: Stroke thrombolysis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Categorical shift in modified Rankin Scale score at 3 months | Categorical shift towards better stroke outcome as reflected by lower, i.e. better, Rankin Scale scores over the range of the scale in active compared to control group. | 90 (range 76-104) days from stroke onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional independence at 3 months after stroke onset | Proportion of patients with functional independence (modified Rankin Scale, mRS, score 0-2) at 3 months after stroke onset | 90 (76-104) days after stroke onset | 
| Excellent recovery at 3 months | Proportion of patients with excellent outcome (mRS score 0-1) at 3 months | 90 (76-104) days after stroke onset | 
| Length of in-hospital stay | Days to discharge from in-hospital ward to home/secondary care for survivors in thrombectomy vs. control | 90 (76-104) days after stroke onset | 
| Home time stay | Number of days the patient stayed at home or at relative's stay within the first 3 months after stroke onset, in thrombectomy vs. control | 90 (76-104) days after stroke onset | 
| Recurrent stroke within 3 months |  | 90 (76-104) days after stroke onset | 
| Recanalisation of the occluded artery for thrombectomy treated population | Recanalisation of the occluded artery for thrombectomy treated population, defined as at least TICI 2b flow in the treated territory after procedure | 6h | 
| Time to revascularisation | Time from stroke onset to revascularisation to any TICI (Thrombolysis in Cerebral Infarction) grade (2b-3 by core lab evaluation) for the actively treated population | 6h | 
| Recanalisation of the occluded artery at 24h computerized tomography angiography /contrast-enhanced magnetic resonance angiography | Defined as AOL 2-3 | 22-36h | 
| Proportion of patients with recanalisation before thrombectomy | Defined as AOL 2-3 | 6h | 
| Reduction of infarct size | Reduction in infarct size (thrombectomy vs. control) at 22-36 hours | 22-36h | 
| Neurological and functional improvement in relation to thrombus length | Neurological improvement (difference in National Institute of Health Stroke Scale from baseline to 12h, to 24h and to 7D after initiation of intravenous thrombolysis, or discharge if earlier), and functional outcome at 3 months in relation to recanalisation status and thrombus length (mm) | 90 (76-104) days | 
| All-cause mortality at 3 months |  | 90 (76-104) days | 
| Neurological death within 7 days post treatment |  | 7 days | 
| Distal embolism/reocclusion demonstrated by follow-up computerized tomography angiography /contrast-enhanced magnetic resonance angiography | Distal embolism/reocclusion will be evaluated by DSA immediately following the endovascular intervention and at the 22-36 hour follow up CT and CTA scans. The proportion of patients with recanalisation of the target occlusion and distal enbolism/reocclusion will be calculated. | 22-36h | 
| Embolism into new territories (ENT) |  | 22-36h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Cerebrovascular Accident, Brain ischemia, Intravenous thrombolysis, Stroke thrombectomy, Stent-retriever