CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).

Study Overview
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Brief Summary
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Multi-center, randomized, parallel-group, superiority study to compare the efficacy of adjunct intra-arterial rt-PA versus not adjunct intra-arterial rt-PA in the improvement of the efficacy of mechanical thrombectomy in patients with large vessel occlusion acute ischemic stroke.

Detailed Description
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The study objective is to validate whether the administration of intra-arterial rt-PA is efficient as an add-on to mechanical thrombectomy in patients with acute ischemic stroke and complete or near-complete recanalization of a proximal vessel occlusion and successful brain reperfusion on cerebral angiogram (corresponding to modified treatment in cerebral infarct (mTICI) score 2b/3). Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation treated with MT resulting in a mTICI score 2b/3 on cerebral angiography will be enrolled in the angiosuite by interventionalists or neurologists once a mTICI 2b/3 is confirmed on cerebral angiography. Each included patient will be followed up to 90 days from the stroke. The primary outcome is the proportion of patients with microvascular hypoperfusion on CT Perfusion at 36±24h. The key secondary outcome is the proportion of patients with a mRS 0 to 1 at 90 days

Official Title
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CHemical OptImization of Cerebral Embolectomy in Patients With Acute Stroke Treated With Mechanical Thrombectomy 2 (CHOICE 2 TRIAL)

Conditions
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Stroke, Acute Ischemic, Stroke, Acute

Intervention / Treatment
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* Drug: Intraarterial alteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic large vessel occlusion (LVO) in the anterior circulation (ICA, ACA or MCA) treated with MT resulting in a mTICI score 2b/3 at end of the procedure. Patients with a mTICI score 2b/3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study. Estimated delay to onset of rescue intraarterial rt-PA administration <24 hours from symptom onset, defined as the point in time the patient was last seen well. No significant pre-stroke functional disability (modified Rankin scale 0-1), or mRS >1 that according to the investigator is not related to neurological disease (i.e., amputation, blindness) Age ≥18 ASPECTS >6 on non-contrast CT (NCCT) scan if symptoms lasting <4.5 hours of last seen well. In patients with >4.5h of last seen well, a CT-perfusion (Flow maps) or MRI-perfusion should be considered instead of NCCT, especially if >9h have elapsed, or in seriously ill patients (i.e., NIHSS>17). Nonetheless, if a perfusion study is not available, NCCT can still be used as long as it is confirmed without a doubt that the ASPECTS is > 6. Informed consent, obtained from patient or acceptable patient surrogate, or Differed Informed Consent (DIC) to avoid any delay in the initiation of the mechanical thrombectomy and the i.a thrombolysis. The DIC will be signed by the patient or acceptable patient surrogate at any time after the tPA treatment is started. Exclusion Criteria: NIHSS score on admission >25 Contraindication to IV t-PA as per local national guidelines (except time to therapy) Use of carotid artery stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h Need of more than 3 passes (per vessel) or more than a total of 5 passes (in more than one vessel) to complete the endovascular procedure Female who is pregnant or lactating or has a positive pregnancy test at time of admission Current participation in another investigation drug or device treatment study Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency Known coagulopathy, INR > 1.7 Platelets < 50,000 Renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30 Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason Any hemorrhage on CT/MRI Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal Suspicion of aortic dissection Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol History of life-threatening allergy (more than rash) to contrast medium SBP >185 mmHg or DBP >110 mmHg refractory to treatment Serious, advanced, terminal illness with anticipated life expectancy < 6 months Pre-existing neurological or psychiatric disease that would confound evaluation Presumed vasculitis or septic embolization Unlikely to be available for 90-day follow-up (i.e., no fixed home address, visitor from overseas)

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, prospective, randomized, open, blinded end-point assessment phase III trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intraarterial alteplase<br>All the patients will be given a 15 minutes IA infusion of alteplase (Actylise®) at a drug concentration of 1.0 mg/ml. At 15 minutes of IA treatment onset, the infusion will be stopped and the angiographic score assessed. Study drug will be prepared according to the following steps: 1/ Dilute 2 vials of 10 mgs (rt-PA) in 20 cc of sterile water for injection (SWI), to attain a 20 ml solution at a concentration of 1mg/ml; 2. Calculate the volume of cc of infusion and therefore the total dose as per the formula: (Patient's weight in Kgs multiplied by 0.225). A patient of 89 Kgs or more will receive 20.0 cc of infusion for 15 min, totaling a dose of 20.0 mg of rt-PA. | Drug: Intraarterial alteplase<br>* See arm/group descriptions.<br>* Other names: Intraarterial recombinant tissue plasminogen activator (rt-PA);|
| No Intervention: No intervention<br>Patients allocated to this arm will receive a similar care to patients allocated to IA alteplase except the thrombolytic | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microvascular hypoperfusion on brain CT Perfusion | Proportion of patients with abnormal microvascular hypoperfusion on brain CTPerfusion at 36±24hours post Mechanical Thrombectomy. | 36±24hours post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified Rankin Scale (mRS) score | Proportion of patients with a mRS 0 to 1 (min value 0, max value 6, higher score worse outcome) | 90 days post MT | 
| Volume of microvascular hypoperfusion on follow-up brain CTP | Volume of hypoperfusion on brain CTP at 36h±24hours post MT | 36±24hours post treatment | 
| Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP | Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP at 36±24hours post MT. | 36±24hours post treatment | 
| Barthel Scale score | Barthel Scale score of 95 to 100, (min value 0, max value 100, higher score better outcome) | day 90 post treatment | 
| EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) | Quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) The score has five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. | day 90 post treatment | 
| Shift analysis of the modified Rankin Scale (mRS) | Shift analysis of the modified Rankin Scale (mRS), at day 90 (min value 0, max value 6, higher score worse outcome) | day 90 post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical Thrombectomy, Recanalization, Reperfusion, Alteplase