Intraarterial Alteplase Versus Placebo After Mechanical Thrombectomy
- Registration Number
- NCT03876119
- Lead Sponsor
- Hospital Clinic of Barcelona
- Brief Summary
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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
Not provided
Not provided
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. 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) Placebo Placebo 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)
- Primary Outcome Measures
Name Time Method Good outcome at 90 days Day 90 after treatment. The primary outcome will be the proportion of patients with a mRS 0 to 1 at 90 days
- Secondary Outcome Measures
Name Time Method Shift analysis of the 90-day modified Rankin Scale (mRS). Day 90 after treatment. The shift analysis of the modified Rankin Scale (mRS), at day 90. The mRS at 90 days will be analyzed using a proportional odds model (POM) that combine into single worst rank the last two categories (5: severe incapacity and 6: death).
Infarct expansion ratio. 48 (+/- 24h) hours of stroke Infarct Expansion Ratio on DWI-MRI (continuous variable), at 48h (+/- 24h) of stroke
Rate of infarct expansion at 24 hours. 48 (+/- 24h) hours of stroke Proportion of patients with/without infarct expansion (dichotomous variable).
Final infarct volume. 48 (+/- 24h) hours of stroke Infarction Volume on Diffusion Weighted Imaging (Magnetic Resonance Imaging) at 48h (+/- 24h) of stroke onset
TERTIARY OUTCOME: Barthel Scale at day 90 Day 90 after treatment. Barthel Scale score of 95 to 100, at day 90
Angiographic improvement on the Arterial Occlusive Lesion (AOL) scale 10 minutes after treatment Proportion of patients with angiographic improvement on the Arterial Occlusive Lesion (AOL) scale. AOL describes arterial patency at the site of occlusion based on the degree of luminal opening (none, partial, or complete) with further qualification based simply on the presence (grades 2 or 3) or absence (grades 0 or 1) of any downstream flow.
TERTIARY OUTCOME: Ischemic worsening within 72 hours os stroke onset 72 hours of stroke onset Ischemic worsening (≥ 4 points in the NIHSS score) within 72 hours of stroke onset not attributable to stroke recurrence
TERTIARY OUTCOME: Quality of life measured at 90 days Day 90 after treatment. Quality of life measured with the EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D-3L) at 90 days
Trial Locations
- Locations (7)
Germans Trias i Pujol Hospital
🇪🇸Badalona, Spain
Hospital Clinic of Barcelona
🇪🇸Barcelona, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital Josep Trueta (HJT)
🇪🇸Girona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain