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
- Phase
- Phase 2
- Status
- Not yet recruiting
- Sponsor
- Beijing Tiantan Hospital
- Enrollment
- 159
- Locations
- 1
- Primary Endpoint
- Infarct core growth reduction via magnetic resonance imaging (MRI) at 5-7 days
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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;
Arms & Interventions
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.
Intervention: High-dose Anakinra (Drug)
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.
Intervention: Low-dose Anakinra (Drug)
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.
Intervention: Standard medical treatment (Other)
Outcomes
Primary Outcomes
Infarct core growth reduction via magnetic resonance imaging (MRI) at 5-7 days
Time Frame: 5-7 days
Secondary Outcomes
- Ordinal distribution of modified Rankin Scale (mRS) at 90 days(90 days)
- The proportion of patients who have a score of 0 or 1 on the modified Rankin Scale (mRS) at 90 days(90 days)
- The proportion of patients with an modified Rankin Scale (mRS) score of 0-2 at 90 days(90 days)
- The proportion of patients with an modified Rankin Scale (mRS) score of 5-6 at 90 days(90 days)
- The rate of early neurological improvement at 72 hours(72 hours)
- The median value of change in the National Institute of Health Stroke Scale (NIHSS) score at 7 days(7 days)
- The proportion of complete recanalization at 24 hours after randomization(24 hours)
- The proportion of improvement on reperfusion at 24 hours after randomization(24 hours)
- The proportion of symptomatic intracranial hemorrhage(36 hours)
- Malignant stroke resulting in herniation and craniectomy within 7 days(7 days)
- The proportion of all-cause mortality(90 days)
- The proportion of serious adverse events (SAEs)(90 days)
Investigators
Yunyun Xiong
Professor
Beijing Tiantan Hospital