Cerebral Edema, Ischemic Stroke, Acute, Malignant Cerebral Edema, Anterior Circulation Brain Infarction
Conditions
Brief summary
The primary objective is to investigate whether treatment with Adacolumn can ameliorate the progression of cerebral edema within 72 hours in patients with anterior circulation ischemic stroke. The secondary objective is to explore if Adacolumn could improve acute neurologic status, functional outcomes, treatment requirements and safety in patients with anterior circulation ischemic stroke.
Detailed description
This is a prospective, randomized, controlled trial evaluating Adacolumn therapy in patients with acute ischemic stroke due to anterior circulation large-artery occlusion presenting within 10 hours of stroke onset. Eligible patients who meet all inclusion and no exclusion criteria will be randomized in a 1:1 ratio to the Adacolumn group or the control group, with 5 patients enrolled in each arm (total n=10). All participants will have undergone guideline-based endovascular thrombectomy for acute ischemic stroke, together with standard medical management. In the Adacolumn group, each patient will undergo four scheduled Adacolumn treatment sessions in addition to endovascular thrombectomy and standard medical therapy. Patients in the control group will receive endovascular thrombectomy and standard medical treatment alone. Each participant will be followed for 90 days after enrollment. The objective of the trial is to evaluate the effect of Adacolumn therapy on cerebral edema in patients with anterior circulation large-artery occlusion stroke. The primary endpoint is the change in net water uptake (NWU) measured on CT at 72-78 hours post reperfusion, compared to the immediate post-reperfusion CT.
Interventions
DEVICEAdacolumn®
Adacolumn treatment ：once a day for 4 consecutive days after enrollment (60 minutes each time, blood flow rate 30 mL/min, total blood volume processed 1800 mL); the treatment was performed by establishing extracorporeal circulation through bilateral arm veins, and a total of 4 adsorption treatments were completed.
PROCEDUREEndovascular Thrombectomy
Endovascular thrombectomy will be performed in strict accordance with the indications, contraindications, and operational specifications outlined in the Chinese Stroke Society Guidelines for Reperfusion Therapy in Acute Ischemic Stroke (2024), as well as the latest official instructions for use of the relevant endovascular devices and adjunctive medications.
Standard medical management for ischemic stroke.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-80 years, regardless of gender; 2. A clinical diagnosis of acute ischemic stroke; 3. Proven large vessel occlusion in ICA or MCA-M1 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) determined by MRA or CTA or DSA; 4. NIHSS score ≥10 at screening; 5. Pre-stroke mRS score \<2 (independent in all activities of daily living); 6. Time from stroke onset to initiation of the first Adacolumn treatment is ≤10 hours, stroke onset is defined as the last time the patient was known to be at their neurological baseline (wake-up strokes qualify if within this time window); 7. All endovascular thrombectomy procedures must strictly adhere to the "2024 Chinese Stroke Association Guidelines for Reperfusion Therapy in Acute Ischemic Stroke" and the latest prescribing information/instructions for use regarding indications, contraindications, and procedural standards; 8. Written informed consent obtained from the patient or legally authorized representative.
Exclusion criteria
1. Decompressive craniectomy performed before enrollment or between enrollment and initiation of study treatment; 2. Patients who receive intravenous thrombolysis (including bridging therapy) for the index ischemic stroke episode before or during endovascular thrombectomy; or undergo permanent intracranial or extracranial stent implantation (including intracranial stent-assisted thrombectomy or carotid stenting) during the index endovascular procedure; 3. After endovascular thrombectomy: extensive contrast extravasation (diffuse subarachnoid high density or parenchymal high density not consistent with hematoma), new subarachnoid hemorrhage（SAH）, or symptomatic intracranial hemorrhage (sICH); 4. Large-vessel occlusion is attributed to other determined etiologies per TOAST classification, such as tumor-related, dissection-related, or other clearly identifiable non-LAA/non-CE causes. 5. Clinical signs of brain herniation, such as unilateral or bilateral fixed dilated pupils and/or other loss of brainstem reflexes attributable to cerebral edema or herniation in the investigator's opinion; 6. Intracranial lesions conferring markedly increased bleeding risk (known brain tumor, arteriovenous malformation, aneurysm); 7. Inability to undergo MRI; 8. Absolute neutrophil count \<1.5×10⁹/L or \>15×10⁹/L 9. Absolute monocyte count \> 1.0 ×10⁹/L; 10. Red blood cells \<3.0×10¹²/L ; 11. Active internal bleeding or bleeding tendency (such as platelet count \<100×10⁹/L, INR \>1.7, PT \>15 seconds); 12. Marked hypercoagulability (fibrinogen \>700 mg/dL); 13. Intracranial or spinal surgery or severe head trauma within the past 3 months; 14. Refractory hypertension (persistent systolic blood pressure \>185 mmHg or diastolic \>110 mmHg); 15. Known allergy to components of the blood purification system (including adsorption membrane, anticoagulants); 16. Acute ST-segment elevation myocardial infarction and/or acute decompensated heart failure and/or corrected QT interval \>520 ms and/or history of cardiac arrest within the past 6 months(pulseless electrical activity, ventricular tachycardia, ventricular fibrillation, or asystole); 17. Body temperature \>38°C or active infection; 18. Active autoimmune disease or immunodeficiency; 19. Participation in another interventional clinical trial within the past 30 days; 20. Any other condition deemed unsuitable for participation by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The change in net water uptake (NWU) on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion | 72 hours | The change in net water uptake (NWU) measured on CT at 72-78 hours post-reperfusion, compared to the immediate post-reperfusion CT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who underwent decompressive craniectomy (DC) | Baseline up to Day 14 | — |
| modified Rankin Scale (mRS) Score | Day 90 | — |
| Number of participants who achieved mRS 0-2 | Day 90 | — |
| Number of participants who achieved mRS 0-3 | Day 90 | — |
| Number of participants with death | Baseline up to Day 90 | — |
| The relative percentage change in DWI edema volume at day 4 post-reperfusion compared to the immediate post-reperfusion DWI | Day 4 | — |
| The relative percentage change in DWI infarct volume at day 4 post-reperfusion compared to the immediate post-reperfusion DWI | Day 4 | — |
| Change in National Institutes of Health Stroke Scale (NIHSS) score on day 7 post-treatment compared to immediate post-operative baseline | Day 7 | — |
| Serious adverse events (SAEs) related to Adacolumn treatment (Primary Safety Outcome) | Randomization to Day 90 | Adacolumn treatment-related SAEs specifically including but not limited to: hypotension requiring vasopressor support (systolic blood pressure \<90 mmHg); access site hemorrhage or hematoma; infection (manifested as fever or access site erythema); electrolyte disturbances such as hypokalemia or hypocalcemia; thrombocytopenia (platelet count \<100 × 10⁹/L); and any other event judged by the investigator to be a treatment-related SAE. |
| The number of discontinuation of Adacolumn therapy due to adverse events (Safety Outcome) | Randomization up to Day 3 | Record the number of patients who permanently discontinued Adacolumn therapy during the treatment period specifically due to SAEs |
| Number of participants who developed brain herniation after treatment | Baseline up to Day 14 | — |
| The change in midline shift on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion | 72 hours | — |
Countries
China
Contacts
CONTACTJianmin Zhang
CONTACTLigen Shi
Outcome results
None listed