Intraarterial Alteplase Versus Placebo After Mechanical Thrombectomy (CHOICE)

Hospital Clinic of Barcelona

Status and phase: Completed; Phase 3; Phase 2

Conditions: Stroke, Acute

Treatments: Drug: Intraarterial alteplase; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT03876119

CHOICE

Details and patient eligibility

About

Multicenter, randomized, placebo-controlled, double blind, phase 2b trial of acute stroke patients treated with mechanical thrombectomy (MT), in which two therapies are compared: rt-PA or placebo. Allocation at each center will account for 1 stratum: use of alteplase (yes vs. no) before MT. Subjects will be followed up to 90 days post-randomization.

Full description

The study objective is to evaluate whether rt-PA is safe and 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 mTICI score 2b/3) The study is a multicenter, randomized, placebo-controlled, double blind, phase 2b trial of acute stroke patients treated with MT, in which two therapies are compared: rt-PA or placebo. Allocation at each center will account for 1 stratum: use of alteplase (yes vs. no) before MT. Subjects will be followed up to 90 days post-randomization

Patients will be enrolled in the angiosuit by interventionalists or neurologists once a mTICI 2b/3 is confirmed on cerebral angiography. The primary outcome is the proportion of patients with a mRS 0 to 1 at 90 days. A sample size of 100 patients per treatment arm in a 1:1 allocation will have at least 80% statistical power for the primary outcome (mRS with 0-1 score values) assuming a rate of 40% in the control arm and a 21% benefit in the experimental arm (odds ratio (OR) of 2.33) for a 5% two-sided type I error. This sample size will also guarantee the study power for that relative treatment benefit even if the success rate in the control group rises up to ≈56%. No study losses are accounted for since all randomised patients will be included in the analysis.

Enrollment: 121 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with symptomatic large vessel occlusion (LVO) in the anterior, middle or posterior cerebral artery treated with MT resulting in an mTICI score 2b/3 at end of the procedure.. Patients with an mTICI score 2b/3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.
2. 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
3. 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)
4. Age ≥18
5. ASPECTS >6 on non-contrast CT (NCCT) scan or MRI if symptoms lasting <4.5 hours or ASPECTS >6 on CT-Perfusion (CTP) or DWI-MRI if symptoms >4.5 <24 hours.
6. Informed consent obtained from patient or acceptable patient surrogate

Exclusion criteria

1. NIHSS score on admission >25
2. Contraindication to IV t-PA as per local national guidelines (except time to therapy)
3. Use of carotid artery stents during the endovascular procedure requiring dual antiplatelet therapy during the first 24h
4. Female who is pregnant or lactating or has a positive pregnancy test at time of admission
5. Current participation in another investigation drug or device treatment study (except observational study i.e.: RACECAT or clinical trials not testing new medical devices or new drugs i.e.IMAGECAT)
6. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
7. Known coagulopathy, INR > 1.7 or use of novel anticoagulants < 48h from symptom onset
8. Platelets < 50,000
9. Renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] < 30
10. Subject who requires hemodialysis or peritoneal dialysis, or who have a contraindication to an angiogram for whatever reason
11. Any hemorrhage on CT/MRI
12. Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT or MRI scan is normal
13. Suspicion of aortic dissection
14. Subject currently uses or has a recent history of illicit drug(s) or abuses alcohol
15. History of life threatening allergy (more than rash) to contrast medium
16. SBP >185 mmHg or DBP >110 mmHg refractory to treatment
17. Serious, advanced, terminal illness with anticipated life expectancy < 6 months
18. Pre-existing neurological or psychiatric disease that would confound evaluation
19. Presumed vasculitis or septic embolization
20. Unlikely to be available for 90-day follow-up (e.g. no fixed home address, visitor from overseas)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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121 participants in 2 patient groups, including a placebo group

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. If the angiographic score is improved compared with the baseline score the procedure is terminated, otherwise a new angiographic series will be repeated in 10 minutes before the end of the procedure in front and profile projections. Study drug will be prepared according to the following steps: 1. Dilute 3 vials of 10 mgs (alteplase) in 30 cc of sterile water for injection (SWI), to attain a 30 cc 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)

Treatment:

Drug: Intraarterial alteplase

Placebo

Placebo Comparator group

Description:

The placebo will consist of a lyophilized white powder containing 0.2 mol/L arginine phosphate, 0.01% polysorbate 80, and pH 7.4 after reconstitution. Study drug will be prepared according to the following steps: 1. Dilute 3 vials of 10 mgs (placebo) in 30 cc of sterile water for injection (SWI), to attain a 30 cc 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)

Treatment:

Drug: Placebo