Endovascular Treatment, Stroke Acute
Conditions
Keywords
acute ischemic stroke, endovascular treatment, successful recanalization, Anakinra
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.
Interventions
DRUGHigh-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.
DRUGLow-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.
OTHERStandard medical treatment
Administration of standard medical treatment should be done according to routine clinical practice and current international guidelines.
Sponsors
Beijing Tiantan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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; * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Infarct core growth reduction via magnetic resonance imaging (MRI) at 5-7 days | 5-7 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ordinal distribution of modified Rankin Scale (mRS) at 90 days | 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. |
| 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 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. |
| 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 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. |
| The proportion of patients with an modified Rankin Scale (mRS) score of 5-6 at 90 days | 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. |
| The rate of early neurological improvement at 72 hours | 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. |
| The median value of change in the National Institute of Health Stroke Scale (NIHSS) score at 7 days | 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. |
| The proportion of complete recanalization at 24 hours after randomization | 24 hours | Complete recanalization is defined as an Arterial Occlusion Lesion scale \[AOL\] score of 3 (scale range, 0 \[no recanalization\] to 3 \[complete recanalization\]). |
| The proportion of improvement on reperfusion at 24 hours after randomization | 24 hours | Improvement on reperfusion is defined as \>90% reduction in Tmax \> 6s lesion volume |
| The proportion of symptomatic intracranial hemorrhage | 36 hours | Symptomatic intracranial hemorrhage within 36 hours (as defined by Safe Implementation of Thrombolysis in Stroke Monitoring Study \[SITS-MOST\] criteria) |
| Malignant stroke resulting in herniation and craniectomy within 7 days | 7 days | Malignant stroke resulting in herniation and craniectomy within 7 days |
| The proportion of all-cause mortality | 90 days | All-cause mortality at 90 days |
| The proportion of serious adverse events (SAEs) | 90 days | Serious adverse events within 90 days |
Countries
China
Contacts
CONTACTYunyun Xiong, professor
PRINCIPAL_INVESTIGATORYunyun Xiong
Beijing Tiantan Hospital
Outcome results
None listed