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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cerebral Edema; Ischemic Stroke, Acute; Malignant Cerebral Edema; Anterior Circulation Brain Infarction
• Intervention / Treatment: Device: Adacolumn®; Procedure: Endovascular Thrombectomy; Drug: Standard medical management

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jianmin Zhang; Phone Number: +86 13805722695; Email: zjm135@zju.edu.cn
• Study Contact Backup: Name: Ligen Shi; Phone Number: +86 13732233245; Email: slg0904@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 311221
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Jianmin Zhang; Phone Number: +86 13805722695; Email: zjm135@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 ≤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);
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Device: Adacolumn®; Adacolumn Treatment Combined with Endovascular Thrombectomy and Standard Medical Therapy	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: Endovascular 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.; Drug: Standard medical management; Standard medical management for ischemic stroke.
Active Comparator: Standard Treatment; Endovascular Thrombectomy and Standard Medical Therapy	Procedure: Endovascular 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.; Drug: Standard medical management; Standard medical management for ischemic stroke.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in net water uptake (NWU) on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion	The change in net water uptake (NWU) measured on CT at 72-78 hours post-reperfusion, compared to the immediate post-reperfusion CT	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale (mRS) Score		Day 90
Serious adverse events (SAEs) related to Adacolumn treatment (Primary Safety Outcome)	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.	Randomization to Day 90
The number of discontinuation of Adacolumn therapy due to adverse events (Safety Outcome)	Record the number of patients who permanently discontinued Adacolumn therapy during the treatment period specifically due to SAEs	Randomization up to Day 3
The change in midline shift on CT between the immediate post-reperfusion and 72-78 hours post-reperfusion		72 hours
Change in National Institutes of Health Stroke Scale (NIHSS) score on day 7 post-treatment compared to immediate post-operative baseline		Day 7
Number of participants who developed brain herniation after treatment		Baseline up to Day 14
Number of participants who underwent decompressive craniectomy (DC)		Baseline up to Day 14
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dynamic changes in peripheral blood immune cells before and after Adacolumn therapy		Baseline up to Day 3、 Day 7
Cerebral immune cell infiltration analysis	For patients undergoing decompressive craniectomy combined with internal decompression, intraoperative brain tissue samples will be collected from the infarct region. These specimens will be subjected to comprehensive analysis to characterize the infiltration, including quantification, phenotypic identification, and functional assessment of immune cells	Baseline up to Day 14

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

General Publications

• 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.
• 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: 10.1093/ecco-jcc/jjw032. Epub 2016 Jan 27.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 3, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Ischemia; Infarction; Necrosis; Ischemia; Stroke; Pathological Conditions, Signs and Symptoms; Ischemic Stroke; Brain Edema; Brain Infarction
• Other Study ID Numbers: 2025-1867

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes