Stroke, Acute, Stroke, Acute Ischemic
Conditions
Keywords
Mechanical Thrombectomy, Recanalization, Reperfusion, Alteplase
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.
Interventions
See arm/group descriptions.
Sponsors
Hospital Clinic of Barcelona
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The evaluation of the primary outcome measure (modified Rankin Scale Score 0-1 at day 90) will be conducted by central blinded evaluators following a structured questionnaire. The evaluation of imaging outcome measures will be conducted at the Imaging Central Core Laboratory by blinded evaluators
Intervention model description
Multicenter, prospective, randomized, open, blinded end-point assessment phase III trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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) |
| Barthel Scale score | day 90 post treatment | Barthel Scale score of 95 to 100, (min value 0, max value 100, higher score better outcome) |
Other
| Measure | Time frame | Description |
|---|---|---|
| SAFETY OUTCOME: Mortality at 90 days | Day 90 | Mortality at 90 days |
| SAFETY OUTCOME: symptomatic intracerebral hemorrahge (sICH ) rate at 24 hours. | 24hours post MT | Symptomatic ICH will be classified as per the European Cooperative Acute Stroke Study (ECASS) 3 criteria |
Countries
Spain
Outcome results
None listed