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

Official title

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)

Overview

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.

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.

Interventions

• 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.
• 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
  Administration of standard medical treatment should be done according to routine clinical practice and current international guidelines.

Primary outcome measures

• Infarct core growth reduction via magnetic resonance imaging (MRI) at 5-7 days [Time frame: 5-7 days]

Secondary outcome measures (12)

• Ordinal distribution of modified Rankin Scale (mRS) at 90 days [Time frame: 90 days]
• The proportion of patients who have a score of 0 or 1 on the modified Rankin Scale (mRS) at 90 days [Time frame: 90 days]
• The proportion of patients with an modified Rankin Scale (mRS) score of 0-2 at 90 days [Time frame: 90 days]
• The proportion of patients with an modified Rankin Scale (mRS) score of 5-6 at 90 days [Time frame: 90 days]
• The rate of early neurological improvement at 72 hours [Time frame: 72 hours]
• The median value of change in the National Institute of Health Stroke Scale (NIHSS) score at 7 days [Time frame: 7 days]
• The proportion of complete recanalization at 24 hours after randomization [Time frame: 24 hours]
• The proportion of improvement on reperfusion at 24 hours after randomization [Time frame: 24 hours]
• The proportion of symptomatic intracranial hemorrhage [Time frame: 36 hours]
• Malignant stroke resulting in herniation and craniectomy within 7 days [Time frame: 7 days]
• The proportion of all-cause mortality [Time frame: 90 days]
• The proportion of serious adverse events (SAEs) [Time frame: 90 days]

Eligibility criteria

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.

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

• Beijing tiantan hospital — Beijing

Identifiers

NCT: NCT07423975 · 2025-B15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗