CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2).
- Conditions
- Stroke, AcuteStroke, Acute Ischemic
- Interventions
- Registration Number
- NCT05797792
- Lead Sponsor
- Hospital Clinic of Barcelona
- Brief Summary
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
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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 440
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intraarterial alteplase Intraarterial alteplase 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.
- Primary Outcome Measures
Name Time Method Modified Rankin Scale at day 90 90 days post treatment Proportion of patients with Modified Rankin Scale 0 or 1 at day 90 +/- 15d
- Secondary Outcome Measures
Name Time Method Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP 36±24hours post treatment Infarct Expansion Ratio (IER): Final infarct to initial ischemic tissue volumes on brain CTP at 36±24hours post MT.
Microvascular hypoperfusion on follow-up brain CTP 36±24hours post treatment Proportion of patients with abnormal microvascular hypoperfusion on CT Perfusion
Volume of hypoperfusion on brain CTP at 36h±24h post treatment Volume of hypoperfusion on brain CTP
Barthel Scale score day 90 post treatment Barthel Scale score of 95 to 100, (min value 0, max value 100, higher score better outcome)
EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) day 90 post treatment 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.
Shift analysis of the modified Rankin Scale (mRS) day 90 post treatment Shift analysis of the modified Rankin Scale (mRS), at day 90 (min value 0, max value 6, higher score worse outcome)
Trial Locations
- Locations (14)
Hospital Universitario Dr. Balmis
🇪🇸Alicante, Spain
Hospital Germans Trías i Pujol
🇪🇸Badalona, Spain
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Josep Trueta
🇪🇸Girona, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Univesitario y Politénico La Fe
🇪🇸Valencia, Spain
Hospital Universitario de Valladolid
🇪🇸Valladolid, Spain
Hospital Universitario de Cruces
🇪🇸Bilbao, Spain
Hospital Universitario de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario de A Coruña
🇪🇸Coruña, Spain
Hospital Universitario Son Espases
🇪🇸Mallorca, Spain
Hospital Universitario de Donostia
🇪🇸San Sebastián, Spain