Brain Diseases, Cerebrovascular Disorders, Infarction, Ischemic Stroke, Medium Vessel Occlusion, Nervous System Diseases, Stroke, Vascular Diseases
Conditions
Keywords
Ischemic stroke, Medium vessel occlusion, Stroke, Intra-arterial thrombolysis, Severe stenosis
Brief summary
Acute ischemic stroke (AIS) due to medium vessel occlusion (MeVO) or severe stenosis poses a significant clinical challenge. Recent large randomized controlled trials, DISTAL and ESCAPE-MeVO, demonstrated no significant benefit of endovascular therapy in patients with MeVO. Although intra-arterial thrombolysis has shown promise in clinical experience, robust evidence supporting its efficacy in MeVO or severe stenosis-related AIS is still absent. To fill this gap, the RESCUE MeVO trial has been designed as a multicenter, prospective, randomized, open-label, blinded end-point (PROBE) study to evaluate the efficacy and safety of intra-arterial thrombolysis in patients with AIS caused by MeVO or severe stenosis.
Detailed description
This study is a multicenter, prospective, randomized, open-label, blinded end-point (PROBE) trial. Eligible participants will be adults (age \>18 years) presenting with acute ischemic stroke (AIS) due to MeVO or severe stenosis (≥70%). Participants who meet all inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 ratio to one of two treatment arms. The control group will receive best medical management alone, while the intervention group will receive best medical management in combination with intra-arterial thrombolysis. Intra-arterial thrombolysis is performed by infusing rhTNK-tPA (Tenecteplase) proximal to the occlusion or severe stenosis for 5-30 minutes, with the decision to continue beyond the first 5 minutes being guided by intraprocedural DSA. The primary objective of this study is to evaluate the efficacy and safety of intra-arterial thrombolysis in patients with acute ischemic stroke caused by MeVO or severe stenosis. The primary endpoint is excellent outcome at 90 days, defined as a score of 0-1 on the modified Rankin Scale (mRS).
Interventions
DRUGBest Medical Treatment
Patients in this group will receive standard medical therapy in accordance with the guideline-directed management for acute ischemic stroke.
PROCEDUREIntra-arterial Thrombolysis
rhTNK-tPA（Tenecteplase）dose: 0.4 - 1.2mg/min, maximum dose: 16mg. Patients who have not received IVT are recommended to initiate intra-arterial administration at a rate of 0.8 mg/min, whereas those who have received IVT are recommended to receive 0.4 mg/min. The infusion rate may be dynamically adjusted by the operator according to intra-procedural circumstances, with a maximum rate not exceeding 1.2 mg/min.
Sponsors
The Second Hospital of Anhui Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years * Primary medium vessel occlusion (MeVO) or severe stenosis (≥70%) was detected on CTA, MRA, or DSA, involving arterial segments including M2-M3 of the middle cerebral artery (MCA), A1-A2 of the anterior cerebral artery (ACA), P1-P2 of the posterior cerebral artery (PCA), and the anterior inferior cerebellar artery (AICA), posterior inferior cerebellar artery (PICA), and superior cerebellar artery (SCA) * The clinical symptoms were consistent with MeVO, with a NIHSS score 5 - 25, or an NIHSS score of 3-4 in the presence of disabling neurological deficits (e.g., hemianopia, aphasia, or motor dysfunction) * Intra-arterial thrombolysis was administered within the following time windows: 1. Acute ischemic stroke within 24 hours of symptom onset or last known well, including stroke with known onset, wake-up stroke and stroke with unknown onset, with no obvious hypodensity on CT and good collateral circulation on CTA; 2. Acute ischemic stroke within 24-72 hours of onset, meeting at least one of the following imaging criteria: a.CT or MR perfusion imaging demonstrating target mismatch, defined as an ischemic core volume \<30 mL, a mismatch ratio ≥1.2, and a mismatch volume ≥10 mL.; b.MRI demonstrating DWI-FLAIR mismatch, defined as the presence of acute ischemic lesions on diffusion-weighted imaging (DWI) with no corresponding hyperintense signal on FLAIR, or with FLAIR hyperintense lesions occupying less than one-third of the DWI lesion volume. * Signed informed consent obtained
Exclusion criteria
* Pre-stroke mRS ≥ 2 * Secondary MeVO or severe stenosis caused by endovascular therapy * Neuroimaging demonstrated intracranial hemorrhage, subarachnoid hemorrhage, or other hemorrhagic disorders * Non-contrast CT demonstrating a clearly hypodense lesion corresponding to the vascular territory * Platelet count \<100 × 10⁹/L, known bleeding tendency or coagulation factor deficiency, or oral anticoagulant therapy with an international normalized ratio (INR) \>3.0 * Persistent and uncontrolled hypertension, defined as systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg * History of intracranial hemorrhage within the past 3 months, including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, or subdural hemorrhage * Presence of arteriovenous malformations or brain tumors with mass effect * Gastrointestinal or urinary tract bleeding, or major surgery within the past 3 months * Chronic dialysis or severe renal impairment, defined as a glomerular filtration rate (GFR) \<30 mL/min or serum creatinine \>220 μmol/L (2.5 mg/dL) * Patients with known allergy to thrombolytic agents or their excipients * Patients with known allergy to iodinated contrast agents or other established contraindications * Pregnant or current breastfeeding * Presence of severe systemic comorbidities with a life expectancy of less than 3 months * Deemed unsuitable for participation by the investigator for any reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Excellent outcome | Time Frame: 90 ± 7 days | Number of participants achieving an excellent outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 ± 7 days follow-up. The mRS is a widely used 7-point scale for assessing disability and functional outcomes after stroke, where higher scores represent worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal distribution of mRS | 90 ± 7 days | Ordinal distribution of the modified Rankin Scale (mRS) at 90 ± 7 days. The mRS is a widely used 7-point scale for assessing disability and functional outcomes after stroke, where higher scores represent worse outcomes. |
| Functional independence | Frame: 90 ± 7 days | The proportion of patients achieving functional independence, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 ± 7 days follow-up. The mRS is a widely used 7-point scale for assessing disability and functional outcomes after stroke, where higher scores represent worse outcomes. |
| Poor functional outcome | 90 ± 7 days | Number of participants achieving a poor functional outcome, defined as a modified Rankin Scale (mRS) score of 4-6 at 90 ± 7 days follow-up. The mRS is a widely used 7-point scale for assessing disability and functional outcomes after stroke, where higher scores represent worse outcomes. |
| Early neurological deterioration | 24 ± 12 hours | The proportion of patients with an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score, within 24 ± 12 hours post-randomization. The NIHSS is a standardized 11-item assessment tool designed to quantify neurological deficits in patients with acute stroke. The total score ranges from 0 to 42, with higher values indicating more severe deficits. |
| Any neurological improvement | 24 ± 12 hours | The proportion of patients with a reduction of ≥ 2 points in the National Institutes of Health Stroke Scale (NIHSS) score from baseline at 24 ± 12 hours post-randomization. The NIHSS is a standardized 11-item assessment tool designed to quantify neurological deficits in patients with acute stroke. The total score ranges from 0 to 42, with higher values indicating more severe deficits. |
| Early neurological improvement | 24 ± 12 hours | The proportion of patients with a reduction of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score from baseline at 24 ± 12 hours post-randomization. The NIHSS is a standardized 11-item assessment tool designed to quantify neurological deficits in patients with acute stroke. The total score ranges from 0 to 42, with higher values indicating more severe deficits. |
Countries
China
Contacts
CONTACTQi Li, professor
PRINCIPAL_INVESTIGATORQi Li, professor
The Second Hospital of Anhui Medical University
Outcome results
None listed