CHemical OptImization of Cerebral Embolectomy 2 (CHOICE 2). (CHOICE2)

Hospital Clinic of Barcelona

Status and phase: Enrolling; Phase 3

Conditions: Stroke, Acute; Stroke, Acute Ischemic

Treatments: Drug: Intraarterial alteplase

Study type: Interventional

Funder types: Other

Identifiers

NCT05797792

2023-504262-32 (EudraCT Number)

CHOICE 2

Details and patient eligibility

About

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.

Enrollment: 440 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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440 participants in 2 patient groups

Intraarterial alteplase

Experimental group

Description:

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.

Treatment:

Drug: Intraarterial alteplase

No intervention

No Intervention group

Description:

Patients allocated to this arm will receive a similar care to patients allocated to IA alteplase except the thrombolytic