A Trial of Adacolumn on Cerebral Edema After Anterior Circulation Ischemic Stroke

Official title

Efficacy and Safety of the Adacolumn® Granulocyte and Monocyte/Macrophage Apheresis Device for Cerebral Edema After Acute Anterior Circulation Occlusive Cerebral Infarction: A Prospective, Randomized, Controlled Clinical Trial

Overview

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 24 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 receive guideline-based standard reperfusion therapy (endovascular thrombectomy and/or intravenous thrombolysis, as appropriate) together with standard medical management. In the Adacolumn group, each patient will undergo four scheduled Adacolumn treatment sessions in addition to standard reperfusion and medical therapy. Patients in the control group will receive standard reperfusion therapy 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

• Device Adacolumn®
  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.
• Procedure Standard Reperfusion Therapy
  Endovascular thrombectomy and/or intravenous thrombolysis 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) and the latest official prescribing information for the relevant pharmaceuticals.
• Drug Standard Medical Management
  Standard medical management for ischemic stroke.

Primary outcome measures

• The change in net water uptake (NWU) on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion [Time frame: 72 hours]

Secondary outcome measures (12)

• Serious adverse events (SAEs) related to Adacolumn treatment (Primary Safety Outcome) [Time frame: Randomization to Day 90]
• The number of discontinuation of Adacolumn therapy due to adverse events (Safety Outcome) [Time frame: Randomization up to Day 3]
• The change in midline shift on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion [Time frame: 72 hours]
• Change in National Institutes of Health Stroke Scale (NIHSS) score on day 7 post-treatment compared to immediate post-operative baseline [Time frame: Day 7]
• Number of participants who developed brain herniation after treatment [Time frame: Baseline up to Day 14]
• Number of participants who underwent decompressive craniectomy (DC) [Time frame: Baseline up to Day 14]
• modified Rankin Scale (mRS) Score [Time frame: Day 90]
• Number of participants who achieved mRS 0-2 [Time frame: Day 90]
• Number of participants who achieved mRS 0-3 [Time frame: Day 90]
• Number of participants with death [Time frame: 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 [Time frame: Day 4]
• The relative percentage change in DWI infarct volume at day 4 post-reperfusion compared to the immediate post-reperfusion DWI [Time frame: Day 4]

Eligibility criteria

Inclusion criteria

• Age 18-80 years, regardless of gender;
• A clinical diagnosis of acute ischemic stroke;
• 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;
• NIHSS score ≥10 at screening;
• Pre-stroke mRS score <2 (independent in all activities of daily living);
• Time from stroke onset to initiation of the first Adacolumn treatment is ≤24 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);
• All endovascular thrombectomy and/or intravenous thrombolysis must strictly adhere to the "2024 Chinese Stroke Association Guidelines for Reperfusion Therapy in Acute Ischemic Stroke" and the latest prescribing information regarding indications, contraindications, and procedural standards;
• Written informed consent obtained from the patient or legally authorized representative.

Exclusion criteria

• Decompressive craniectomy performed before enrollment or between enrollment and initiation of study treatment;
• 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);
• 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.
• 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;
• Intracranial lesions conferring markedly increased bleeding risk (known brain tumor, arteriovenous malformation, aneurysm);
• Inability to undergo MRI;
• Absolute neutrophil count <1.5×10⁹/L or >15×10⁹/L
• Absolute monocyte count > 1.0 ×10⁹/L;
• Red blood cells <3.0×10¹²/L ;
• Active internal bleeding or bleeding tendency (such as platelet count <100×10⁹/L, INR >1.7, PT >15 seconds);
• Marked hypercoagulability (fibrinogen >700 mg/dL);
• Intracranial or spinal surgery or severe head trauma within the past 3 months;
• Refractory hypertension (persistent systolic blood pressure >185 mmHg or diastolic >110 mmHg);
• Known allergy to components of the blood purification system (including adsorption membrane, anticoagulants);
• 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);
• Body temperature >38°C or active infection;
• Active autoimmune disease or immunodeficiency;
• Participation in another interventional clinical trial within the past 30 days;
• Any other condition deemed unsuitable for participation by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Publications

• Dignass A, Akbar A, Hart A, Subramanian S, Bommelaer G, Baumgart DC, Grimaud JC, Cadiot G, Makins R, Hoque S, Bouguen G, Bonaz B. Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results. J Crohns Colitis. 2016 Jul;10(7):812-20. doi: PMID 26818659
• Elkins J, Veltkamp R, Montaner J, Johnston SC, Singhal AB, Becker K, Lansberg MG, Tang W, Chang I, Muralidharan K, Gheuens S, Mehta L, Elkind MSV. Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2017 Mar;16(3):217-226. doi: 10.1016/S1474-4422(16)30357-X. Epub 2017 Feb 15. PMID 28229893
• Ren T, Zhu M, Jiang X, Xu L, Jin H, Zhou Y, Zhao Y, Zhuo R, Li W, Chen C, Peng L, Jin X, Li Y, Yang L. Targeting microglial PPARalpha ameliorates the outcome of ischemic stroke by enhancing interaction with infiltrating peripheral monocytes/macrophages. Cell Rep. 2025 Jul 22;44(7):115875. doi: 10.1016/j.celrep.2025.115875. Epub 2025 Jun 20. PMID 40543039
• Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT, Shi FD. Global brain inflammation in stroke. Lancet Neurol. 2019 Nov;18(11):1058-1066. doi: 10.1016/S1474-4422(19)30078-X. Epub 2019 Jul 8. PMID 31296369
• Huttner HB, Schwab S. Malignant middle cerebral artery infarction: clinical characteristics, treatment strategies, and future perspectives. Lancet Neurol. 2009 Oct;8(10):949-58. doi: 10.1016/S1474-4422(09)70224-8. PMID 19747656
• Wu S, Yuan R, Wang Y, Wei C, Zhang S, Yang X, Wu B, Liu M. Early Prediction of Malignant Brain Edema After Ischemic Stroke. Stroke. 2018 Dec;49(12):2918-2927. doi: 10.1161/STROKEAHA.118.022001. PMID 30571414
• Sheth KN, Petersen NH, Cheung K, Elm JJ, Hinson HE, Molyneaux BJ, Beslow LA, Sze GK, Simard JM, Kimberly WT. Long-Term Outcomes in Patients Aged </=70 Years With Intravenous Glyburide From the Phase II GAMES-RP Study of Large Hemispheric Infarction: An Exploratory Analysis. Stroke. 2018 Jun;49(6):1457-1463. doi: 10.1161/STROKEAHA.117.020365. Epub 2018 May 22. PMID 29789393
• Huang X, Yang Q, Shi X, Xu X, Ge L, Ding X, Zhou Z. Predictors of malignant brain edema after mechanical thrombectomy for acute ischemic stroke. J Neurointerv Surg. 2019 Oct;11(10):994-998. doi: 10.1136/neurintsurg-2018-014650. Epub 2019 Feb 23. PMID 30798266

Identifiers

NCT: NCT07386262 · 2025-1867

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗