Advancing Reperfusion Therapy for Ischemic Stroke: Safety and Efficacy of Anakinra for Futile Reperfusion Following Endovascular Treatment in Patients With Acute Ischemic Stroke (ARTS-SAFE)

Advancing Reperfusion Therapy for Ischemic Stroke (ARTS): Safety and Efficacy of Anakinra for Futile Reperfusion Following Endovascular Treatment in Patients With Acute Ischemic Stroke (SAFE)

The investigators initiated a multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled trial to explore the safety and efficacy of different dose of Anakinra compared to standard medical care for patients with acute ischemic stroke who have achieved successful recanalization after endovascular thrombectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Endovascular Treatment; Stroke Acute
• Intervention / Treatment: Drug: High-dose Anakinra; Drug: Low-dose Anakinra; Other: Standard medical treatment

Detailed Description

Adult acute ischemic stroke patients who have achieved successful recanalization (defined as expanded thrombolysis in cerebral infarction [eTICI] 2b50-3) after endovascular thrombectomy within 24 hours of symptom onset will be enrolled in this trial. The enrolled patients have stroke due to Internal carotid artery (ICA), middle cerebral artery (MCA) M1 or M2 occlusions confirmed by CTA/MRA and with baseline National Institutes of Health Stroke Scale (NIHSS) score of 6-25. The eligible patients will be randomly assigned to receive high-dose Anakinra, low-dose Anakinra or standard medical treatment. The primary outcome is Infarct core growth reduction via MRI at 5-7 days.

• Study Type: Interventional
• Enrollment (Estimated): 159
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yunyun Xiong, professor; Phone Number: 86-10-59978350; Email: xiongyunyun@bjtth.org

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tiantan Hospital
      • Contact: Yunyun Xiong, professor; Phone Number: 86-10-59978350; Email: xiongyunyun@bjtth.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age between 18-80 years old (both inclusive);
• Acute ischemic stroke symptom onset within 24 hours; including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
• Pre-stroke modified Rankin scale (mRS) score ≤1;
• Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (both inclusive);
• Internal carotid artery (ICA) or middle cerebral artery (MCA) M1/M2 occlusions confirmed by CTA/MRA and responsible for the signs and symptoms of acute ischemic stroke;
• Successful recanalization (eTICI 2b50-3) after endovascular treatment;
• Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria:

• Allergy to Anakinra;
• NIHSS consciousness score 1a >2, or epileptic seizure, hemiplegia after seizures (Todd's palsy) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate;
• Unable to perform CTP or PWI;
• Acute or past intracerebral hemorrhage (ICH) (including parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, subdural/epidural hematoma) confirmed by CT or MRI;
• Multiple arterial occlusion (e.g., bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);
• Glomerular filtration rate (GFR) <30 mL/min or serum creatinine level >2.5 mg/dL;
• Suspected septic embolism or infective endocarditis;
• Neutropenia (ANC <1.5 × 109/L);
• Known active or recurrent liver disease (including cirrhosis, hepatitis B and C; positive or indeterminate laboratory results), or alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels >3 times the upper limit of normal (ULN) or total bilirubin >2 times ULN;
• History of malignancy other than basal cell carcinoma of the skin;
• History or evidence of active or latent tuberculosis infection, or presence of tuberculosis risk factors including but not limited to: close contact with active tuberculosis patients within the past 12 months;
• Any terminal illness such that the patient would not be expected to survive more than 1 year;
• Pregnant women, nursing mothers, or reluctance to use effective contraceptive measures during the period of trial;
• Unlikely to adhere to the trial protocol or follow-up;
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study;
• Participation in other interventional clinical trials within the previous 3 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-dose Anakinra+standard medical treatment; 100 mg loading dose Anakinra over 60 seconds within 0.5 hours after randomization, followed by consecutive 2mg/kg/h infusions over 24 hours. Standard treatment strategy will be in the discretion of site investigators according to guidelines.	Drug: High-dose Anakinra; 100 mg loading dose Anakinra over 60 seconds within 0.5 hours after randomization, followed by consecutive 2 mg/kg/h infusions over 24 hours.
Experimental: Low-dose Anakinra+standard medical treatment; 100 mg subcutaneous Anakinra over 60 seconds within 0.5 hours after randomization, followed by 100 mg administered twice daily for 3 days. Standard treatment strategy will be in the discretion of site investigators according to guidelines.	Drug: Low-dose Anakinra; 100 mg subcutaneous Anakinra over 60 seconds within 0.5 hours after randomization, followed by 100 mg administered twice daily for 3 days.
Other: Standard medical treatment; All enrolled patients receive standard early management and secondary prevention treatment according to the Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2023.	Other: Standard medical treatment; Administration of standard medical treatment should be done according to routine clinical practice and current international guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Infarct core growth reduction via magnetic resonance imaging (MRI) at 5-7 days	5-7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who have a score of 0 or 1 on the modified Rankin Scale (mRS) at 90 days	The proportion of patients with an mRS score ≤ 1 at 90 days. The mRS score is a seven-point ordered categorical scale from 0 to 6 for functional neurological outcome, with 0 indicating no neurological symptoms and 6 indicating death.	90 days
Ordinal distribution of modified Rankin Scale (mRS) at 90 days	Ordinal distribution of mRS at 90 days (shift analysis). The mRS score is a seven-point ordered categorical scale from 0 to 6 for functional neurological outcome, with 0 indicating no neurological symptoms and 6 indicating death.	90 days
The proportion of patients with an modified Rankin Scale (mRS) score of 0-2 at 90 days	The proportion of patients with an mRS score of 0-2 at 90 days. The mRS score is a seven-point ordered categorical scale from 0 to 6 for functional neurological outcome, with 0 indicating no neurological symptoms and 6 indicating death.	90 days
The proportion of improvement on reperfusion at 24 hours after randomization	Improvement on reperfusion is defined as >90% reduction in Tmax > 6s lesion volume	24 hours
The proportion of complete recanalization at 24 hours after randomization	Complete recanalization is defined as an Arterial Occlusion Lesion scale [AOL] score of 3 (scale range, 0 [no recanalization] to 3 [complete recanalization]).	24 hours
The proportion of patients with an modified Rankin Scale (mRS) score of 5-6 at 90 days	The proportion of patients with an mRS score of 5-6 at 90 days. The mRS score is a seven-point ordered categorical scale from 0 to 6 for functional neurological outcome, with 0 indicating no neurological symptoms and 6 indicating death.	90 days
The rate of early neurological improvement at 72 hours	The rate of early neurological improvement at 72 hours after randomization (defined as a National Institute of Health Stroke Scale [NIHSS] score ≤1 or ≥8 points improvement compared with the baseline). NIHSS is scores range from 0 to 42, with higher scores indicating more severe neurologic deficits.	72 hours
The median value of change in the National Institute of Health Stroke Scale (NIHSS) score at 7 days	The median value of change in the National Institute of Health Stroke Scale (NIHSS) score at 7 days. NIHSS is scores range from 0 to 42, with higher scores indicating more severe neurologic deficits.	7 days
The proportion of symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage within 36 hours (as defined by Safe Implementation of Thrombolysis in Stroke Monitoring Study [SITS-MOST] criteria)	36 hours
Malignant stroke resulting in herniation and craniectomy within 7 days	Malignant stroke resulting in herniation and craniectomy within 7 days	7 days
The proportion of all-cause mortality	All-cause mortality at 90 days	90 days
The proportion of serious adverse events (SAEs)	Serious adverse events within 90 days	90 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yunyun Xiong, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 14, 2026
• First Submitted That Met QC Criteria: February 14, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 14, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: endovascular treatment; acute ischemic stroke; Anakinra; successful recanalization
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Ischemic Stroke; Stroke; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Intercellular Signaling Peptides and Proteins; Cytokines; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: 2025-B15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No