Ultra-early Identification of Futile Recanalization After Reperfusion Therapy in Acute Ischemic Stroke Based on Cerebral Autoregulation

Official title

Ultra-early Identification of Futile Recanalization After Reperfusion Therapy in Acute Ischemic Stroke Based on Cerebral Autoregulation Monitoring: a Multicenter, Prospective, Observational Study

Overview

This multicenter, prospective, observational diagnostic accuracy study enrolls patients undergoing thrombectomy with intraoperative cerebral autoregulation monitoring and follows them up at predefined time points up to 90 days post-enrollment. The study aims to determine whether impaired cerebral autoregulation during thrombectomy can serve as an ultra-early biomarker for predicting futile recanalization in patients with acute ischemic stroke.

Detailed description

Acute ischemic stroke (AIS) is the leading cause of death and disability in China. Landmark randomized controlled trials have demonstrated the benefit of endovascular therapy for patientswith acute stroke due to large-vessel occlusion. Despite successful recanalization rates exceeding 80%, more than half of patients fail to achieve functional independence following thrombectomy a phenomenon termed futile recanalization. Ultra-early identification of futile recanalization is critical for guiding individualized treatment strategies. Timely recognition of at-risk patients may enable targeted interventions - such as intra-arterial thrombolysis, rescue therapy, and neuroprotective measures that could potentially reverse unfavorable outcomes or mitigate adverse events. Monitoring cerebral autoregulation (CA) function during thrombectomy represents a promising approach for the ultra-early prediction of futile recanalization. This multicenter, prospective, observational diagnostic accuracy study aims to validate the hypothesis that intraoperative CA monitoring during thrombectomy can predict futile recanalization. A total of 129 participants will be enrolled and divided into a modeling cohort and a validation cohort. Participants will undergo face-to-face assessments at 24 ± 12 hours, 48 ± 12 hours, and 7 ± 3 days post-enrollment (or at discharge). A follow-up assessment will be conducted via telephone or in-person interview at 90 ± 7 days post-enrollment. The primary endpoints include the sensitivity, specificity, and area under the receiver operating characteristic curve of impaired CA for predicting futile recanalization.

Interventions

• Diagnostic test diagnostic accuracy study
  Cerebral autoregulation is assessed intraoperatively during thrombectomy using near-infrared spectroscopy (NIRS)-derived cerebral oxygen saturation combined with continuous noninvasive or invasive arterial blood pressure monitoring. The correlation between cerebral oxygen saturation and arterial blood pressure is analyzed to quantify cerebral autoregulation status. This monitoring is performed as part of routine clinical care and does not constitute an additional research intervention.

Primary outcome measures

• The sensitivity, specificity and area under the receiver operating characteristic curve for percentage of Modified Rankin scale 0-2 [Time frame: Month 3]

Secondary outcome measures (1)

• The sensitivity, specificity and area under the receiver operating characteristic curve for early neurological improvement [Time frame: Day 1]

Eligibility criteria

Inclusion criteria

• Age ≥ 18
• Clinical signs consistent with acute ischemic stroke with large vessel occlusion in the anterior circulation (intracranial segment of the internal carotid artery, middle cerebral artery M1 segment) demonstrated with CTA/MRA/DSA.
• NIHSS score ≥ 6 obtained prior to endovascular treatment.
• Modified Rankin Scale ≤ 1 prior to qualifying stroke.
• Acute ischemic stroke, undergone endovascular treatment within 24 hours of onset (time of stroke is the last known normal for wake-up stroke or with unknown onset time).with reaching the goal of mTICI grade 2b-3
• For patients with symptom onset within 6 hours: ASPECTS ≥ 3; for patients with symptom onset between 6 and 24 hours: age ≤ 80 years and ASPECTS ≥ 3.
• Patient/Legally Authorized Representative has signed the Informed Consent Form.

Exclusion criteria

• Baseline CT/MRI confirms the presence of multiple vascular territory acute strokes.
• Baseline CT/MRI confirms the presence of arterial dissection.
• Evidence of intracranial hemorrhage or hemorrhagic transformation before thrombectomy.
• Known allergies or intolerances to antiplatelet agents, anticoagulation drugs, iodinated contrast and/or anesthetics.
• Severe infection (e.g. sepsis) or multiple organ failure.
• Known hereditary or acquired hemorrhagic diathesis or coagulation factor deficiency; oral anticoagulant therapy with INR > 3; or use of a factor Xa inhibitor within the preceding 48 hours with an abnormal aPTT.
• Baseline platelet count < 50 × 10\^9/L.
• Blood glucose concentration<50 mg/dL (2.7 mmol/L) or >400 mg/dL (22.2 mmol/L).
• Refractory hypertension that is difficult to control by medication (Defined as persistent systolic blood pressure>185 mmHg or diastolic blood pressure>110 mmHg).
• Severe cardiomyopathy with heart failure (LVEF ≤ 30% or NYHA class IV), acute myocardial infarction, or unstable angina.
• Untreated moderate or severe coronary artery stenosis, or previous coronary artery bypass surgery.
• Current hemodialysis or peritoneal dialysis; known severe renal insufficiency with estimated glomerular filtration rate < 30 mL/min or serum creatinine > 220 μmol/L (2.5 mg/dL).
• Known intracranial aneurysm, and cerebral arteriovenous malformation.
• Malignant brain tumor or CNS infection.
• Pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations (e.g., dementia or mental illness)
• Female who is pregnant or lactating at time of admission.
• Anticipated life expectancy < 6 months.
• Current participation in another investigational drug or device study.
• local skin damage or other conditions that cannot cooperate with electrode sticking.
• severe agitation or other conditions affecting data collection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

China · 4 centers

• Beijing Shijitan Hospital, Capital Medical University — Beijing
• The First Affiliated Hospital of Harbin Medical University — Harbin
• Dalian Municipal Central Hospital — Dalian
• Weifang People's Hospital Affiliated to Weifang Medical University — Weifang

Identifiers

NCT: NCT07556068 · CAREFUL-CA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗