Acute Ischemic Stroke, Anterior Circulation Brain Infarction
Conditions
Keywords
Endovascular thrombectomy, Cerebroprotection, Remote ischemic conditioning
Brief summary
For patients with acute ischemic stroke caused by large vessel occlusion, endovascular thrombectomy has been demonstrated to be the most effective therapy, as approximately 90% of the occluded vessels can be recanalized. However, less than 50% of patients could achieve functional independence, and over 15% died 90 days after stroke. Although the mismatch of successful recanalization with poor prognosis can be attributed to many factors, the infarct core formed during thrombectomy and reperfusion injury after thrombectomy may be among the most important and effective neuroprotective strategies urgently needed. Remote ischemic conditioning (RIC) is a noninvasive strategy in which one or more cycles of brief and transient limb ischemia confer protection against prolonged and severe ischemia in distant organs. In the transient focal cerebral ischemia-reperfusion model, the application of remote ischemic conditioning before reperfusion or both before and after reperfusion reduces reperfusion injuries and the final infarct size. Because patients with acute ischemic stroke who are treated with endovascular thrombectomy can achieve a high rate of recanalization after focal ischemia, this patient population is akin to the model of transient focal cerebral ischemia-reperfusion. Furthermore, a pilot study has determined the safety and feasibility of remote ischemic conditioning in patients undergoing endovascular thrombectomy. However, whether remote ischemic conditioning could provide clinical benefits to patients with acute ischemic stroke who are treated with endovascular thrombectomy urgently needs investigations. This study aims to investigate the safety and efficacy of remote ischemic conditioning in improving functional outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy and explore the effect of treatment duration on the treatment outcome of remote ischemic conditioning.
Interventions
DEVICE14-day remote ischemic conditioning
RIC is a noninvasive therapy performed by an electric auto-control device with a cuff placed on the upper arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of the cuff on the upper arm. The procedure will be performed once before endovascular thrombectomy and twice daily for 14 days post-thrombectomy.
DEVICE30-day remote ischemic conditioning
RIC is a noninvasive therapy performed by an electric auto-control device with a cuff placed on the upper arm. RIC procedures consist of five cycles of 5-min inflation (200 mmHg) and 5-min deflation of the cuff on the upper arm. The procedure will be performed once before endovascular thrombectomy and twice daily for 30 days post-thrombectomy.
PROCEDUREEndovascular thrombectomy
Endovascular thrombectomy procedures are performed according to the guidelines to recanalize the occluded large vessel safely.
Best medical management is prescribed at the discretion of the treating physicians according to the guidelines.
Sponsors
Capital Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age≥18 years； 2. Acute ischemic stroke due to large vessel occlusion in the anterior circulation that is not suitable for intravenous thrombolytic therapy, or has contraindications to intravenous thrombolytic therapy, or treated with intravenous thrombolytic therapy without recanalization; 3. Large vessel occlusion confirmed by computed tomography angiography (CTA) or magnetic resonance angiography (MRA), including the occlusion of the intracranial segment of the internal carotid artery (ICA) and M1 segment of the middle cerebral artery (MCA), is the cause of symptoms, and mechanical thrombectomy is planned within 24 hours from the time last known well; 4. Baseline score of the National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points; 5. Patients or family members signed a written informed consent form.
Exclusion criteria
1. Imaging examination revealed the presence of multiple vascular supply areas of cerebral infarction (such as the simultaneous presence of infarction in both anterior and posterior circulation); 2. Absence of femoral artery pulsation, extremely difficult intravascular access, or extremely tortuous large vessels, which are expected to result in the inability to undergo timely endovascular treatment; 3. Difficult-to-control hypertension: continuous monitoring upon admission shows systolic blood pressure ≥180mmHg, or diastolic blood pressure ≥100mmHg; 4. Coma or lethargy patients (consciousness level score ≥2 in NIHSS); 5. Unable to obtain an accurate baseline NIHSS score; 6. Pre-stroke modified Rankin Scale (mRS) score \>1; 7. Baseline ASPECTS score ≤5; 8. Presence of bleeding tendency, deficiency of coagulation factors, or oral anticoagulant therapy with INR \> 3.0; 9. Baseline blood glucose \<2.7mmol/L or \>22.2mmol/L; 10. Baseline platelet count \< 30\*10\^9/L; 11. Severe known renal impairment defined as requiring dialysis (hemodialysis or peritoneal dialysis), or if known creatinine clearance rate \<30mL/min; 12. Cranial CT or MRI shows intracranial hemorrhage; 13. Cranial CT or MRI shows midline deviation and significant occupying effect; 14. Clinical history, previous imaging examinations, or clinical judgment suggesting intracranial tumors, arteriovenous malformations, or intracranial arterial dissection; 15. History of head injury in the past 3 months; 16. History of life-threatening allergy to contrast agents, nickel, titanium metal, or their alloys; 17. Pregnancy, if women of childbearing age have a positive urinary or serum β-human chorionic gonadotropin (β-hCG) test or are breastfeeding； 18. The life expectancy of patients is less than 6 months, and they cannot be evaluated within 3 months; 19. Limb deformity, soft tissue injury, or other conditions that affect the implementation of distant ischemia adaptation therapy; 20. Participating in other ongoing clinical trials; 21. Other conditions that the investigators believe are not suitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of patients achieving a modified Rankin Scale (mRS) score of 0-2 at 90 days. | 90 days after stroke. | The mRS ranges from 0 to 6, with higher scores indicating worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The ordinal distribution of mRS scores at 90 days. | 90 days after stroke. | The mRS ranges from 0 to 6, with higher scores indicating worse outcomes. |
| The proportion of patients with early neurological improvement 24 hours after endovascular procedures. | 24 hours after endovascular procedures. | The NIHSS ranges from 0 to 42, with higher scores indicating worse outcomes. Neurological improvement is defined as the NIHSS recovering to ≤2 points or decreasing by 8 points or much higher as compared with the baseline. |
| Changes in NIHSS score from baseline to day 14 or at discharge (whichever comes earlier). | 14 days or at discharge (whichever comes first) | The NIHSS ranges from 0 to 42, with higher scores indicating worse outcomes. |
| Score of EQ-5D-5L at 90 days. | 90 days after stroke. | EQ-5D-5L is a tool used to assess health status, including five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A higher score indicates a better health status, while a lower score indicates a poorer health status. |
| Cerebral infarct volume. | 72 hours after endovascular procedures. | The infarction volume will be assessed on cranial CT or MRI imaging. |
| The change of infarct volume. | 72 hours after endovascular procedures. | Infarct Expansion Ratio (IER, IER=infarct volume/baseline infarct volume). The infarction volume will be assessed on cranial CT or MRI imaging, and baseline infarct volume will be assessed on the CTP or baseline MRI imaging. |
| Two dichotomous mRS scores at 90 days (0-1 vs 2-6, 0-3 vs 4-6, 0-4 vs 5-6, 0-5 vs 6). | 90 days after stroke. | The mRS ranges from 0 to 6, with higher scores indicating worse outcomes. |
| Incidence of Symptomatic Intracranial Hemorrhage | Within 14 days after endovascular procedures. | Symptomatic intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging leading to an increase of at least 4 points in the NIHSS score, according to the criteria of the European Cooperative Acute Stroke Study III (ECASS III). |
| Incidence of neurological deterioration within 14 days. | Within 14 days after endovascular procedures. | Neurological deterioration is defined as an increase of ≥4 points in NIHSS compared to before deterioration within 14 days. |
| Incidence of malignant infarction | 0-90 days | Malignant infarction is defined as infarction involving more than half of the affected middle cerebral artery area, a significant mass effect requiring decompressive craniectomy, and/or directly leading to death with clinical signs of brain herniation. |
| All cause of death. | 0-90 days | The incidence of death events at any time from randomization through day 90. |
| Incidence of Adverse Events/Serious Adverse Events | 0-90 days | The incidence of other adverse events and serious adverse events at any time from randomization through day 90. |
| Incidence of intracranial hemorrhage. | Within 14 days after endovascular procedures. | Intracranial hemorrhage is defined as the demonstration of hemorrhage within brain parenchyma on head imaging, according to the criteria of the ECASS III. |
Countries
China
Contacts
Primary ContactXunming Ji, MD, PhD
Backup ContactSijie Li, MD
Outcome results
None listed