Glycemia and Ischemia Reperfusion Brain Injury in Patients With Acute Cerebral Infarction Treated With Mechanical Thrombectomy

Study Overview
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Brief Summary
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Postictus hyperglycemia is associated with an accelerated transformation of the ischemic penumbra into an infarct area, with increased infarct size, worse recanalization, reduced cerebral perfusion, increased ischemia reperfusion damage, and worse outcome. Furthermore, when perfusion is reinstated, hyperglycemia causes secondary tissue damage through an increase in ischemic reperfusion damage. Thus, those patients with glycemia values < 155 mg/dL during mechanical thrombectomy, and especially at the time of reperfusion, will have greater ischemia-reperfusion damage, showing a different profile in miRNA expression, with better neurological and functional outcomes and higher risk of hemorrhagic transformation and cerebral edema. The main objective of the study is to evaluate the association between glycemia values at the time of reperfusion and stroke recovery at 3 months in patients with acute cerebral infarction treated with mechanical thrombectomy.

Official Title
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Glycemia and Ischemia Reperfusion Brain Injury in Patients With Acute Cerebral Infarction Treated With Mechanical Thrombectomy

Conditions
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Cerebral Infarction

Intervention / Treatment
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* Device: Subcutaneous blood glucose monitoring device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over 18 years of age Neuroimaging studies such as computed tomography (CT), angio-CT or angio-MRI compatible with the diagnosis of acute cerebral infarction due to occlusion of a large vessel of the anterior circulation, including the internal carotid artery (intra- or extracranial) or middle cerebral artery (M1 or M2 segments). Indication of mechanical thrombectomy according to clinical practice. Inclusion of the patient in the study before the endovascular procedure. Modified Rankin Scale (mRS) score prior to stroke of 0-1. Signature of informed consent. Exclusion Criteria: CT, angio-CT or angio-MRI showing posterior circulation occlusion. Severe or life-threatening concomitant disease that precludes follow-up for 3 months after stroke, Alcohol or drug abuse Participation in a therapeutic clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Interventional Model Description: Before the start of the endovascular procedure, a subcutaneous blood glucose monitoring device will be implanted, which will be removed on day 15 (or at hospital discharge if this takes place before 15 days). Those patients with blood glucose levels >155 mg/dl will receive insulin at the discretion of the physician responsible for the patient, following the local protocols for the management of hyperglycemia in hospitalized patients and the guidelines for the management of hyperglycemia in patients with acute stroke.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subcutaneous blood glucose monitoring device<br>After signing the informed consent and before the start of the endovascular procedure, a subcutaneous blood glucose monitoring device will be implanted, which will be removed on day 15 (or at hospital discharge if this takes place before 15 days). | Device: Subcutaneous blood glucose monitoring device<br>* After signing the informed consent and before the start of the endovascular procedure, a subcutaneous blood glucose monitoring device will be implanted, which will be removed on day 15 (or at hospital discharge if this takes place before 15 days). This device will be selected from those currently available on the market, with CE marking, and with previous studies documenting its safety and feasibility for radiological procedures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood glucose levels at the time of reperfusion | Blood glucose levels at the time of reperfusion in patients achieving TICI-2b, TICI-2c or TICI3 recanalization pattern after mechanical thrombectomy. | During reperfusion procedure | 
| Modified Rankin scale at 3 months | Its dichotomized assessment (Modified Rankin Scale or mRS 0-2 indicating good functional recovery and 3-6 indicating death or dependence) is commonly used in acute stroke studies. | From baseline to month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak blood glucose values | Peak blood glucose values during the mechanical thrombectomy procedure. | During the mechanical thrombectomy procedure | 
| Blood glucose values above 155 mg/dL | Total time with blood glucose values above 155 mg/dL from arrival at the emergency department to arterial recanalization | The entire time from arrival at the emergency room until completion of the arterial recanalization procedure. | 
| Time in range 110-154 mg/dL of blood glucose values | Time in range 110-154 mg/dL of blood glucose values: (a) from arrival at the emergency department to recanalization; (b) during the first 24 h; and (c) during hospital stay | From arrival at the emergency department to recanalization, during the first 24 hours and during hospital stay | 
| Proportion of patients receiving insulin treatment | Proportion of patients receiving insulin treatment for post-stroke hyperglycemia, during the first 24h from the onset of stroke symptoms | During the first 24 hours from the onset of stroke symptoms | 
| Dose of insulin treatment received by clinical practice | Insulin treatment received by clinical practice (route of administration and dose) | Through study completion, an average of 2 years | 
| Number of subcutaneous blood glucose monitoring devices with technical failures | Number of subcutaneous blood glucose monitoring devices with technical failures (absence or interruption of readings) or requiring replacement due to involuntary removal of the device or inadequate implantation. | Through study completion, an average of 2 years | 
| Additional data of the subcutaneous blood glucose monitoring device | Mean blood glucose | During the time the device is worn, up to 15 days | 
| Number of mechanical thrombectomy passes | Number of mechanical thrombectomy passes (includes aspirations and stent-retriever passes). | Through study completion, an average of 2 years | 
| Degree of recanalization | Degree of recanalization according to the TICI classification in the final angiogram (from no perfusion (grade 0) to complete perfusion (grade 3)) | Through study completion, an average of 2 years | 
| Arterial blood pressure | Arterial blood pressure in the emergencies and at the time of reperfusion. | During reperfusion procedure | 
| Infarct size | Infarct size at 24 hours (assessed by a radiologist who will be unaware of blood glucose monitoring data) | At 24 hours | 
| Hemorrhagic transformation | Hemorrhagic transformation at 24 hours (assessed by a radiologist who will be unaware of blood glucose monitoring data). It will be categorized into four types: (1) hemorrhagic infarction type 1 (HI-1): small petechiae at the edges of the infarcted area; (2) hemorrhagic infarction type 2 (HI-2): confluent petechiae in the infarct area without mass effect; (3) parenchymal hematoma type 1 (HP-1): hematoma occupying ≤ 30% of the infarct area, with discrete mass effect; and (4) parenchymal hematoma type 2 (HP-2): hematoma occupying more than 30% of the infarct area, with evident mass effect. | At 24 hours | 
| Number of symptomatic hemorrhagic transformation | Symptomatic hemorrhagic transformation defined as computed tomography (CT) or Magnetic Resonance Imaging (MRI) evidence of any type of hemorrhage that is accompanied by neurological deterioration ≥ 4 points on the National Institutes of Healt Stroke Scale scale from baseline or leading to death. | During a symptomatic hemorrhagic transformation | 
| National Institutes of Healt Stroke Scale score | National Institutes of Healt Stroke Scale score at 24 hours, at hospital discharge, and at 3 months (scores range from 0 to 42, with higher scores indicating more severe neurological deficit). | At 24 hours and at 3 months | 
| Neurological or systemic complications | Neurological or systemic complications during follow-up. The following complications will be systematically assessed at each visit: coma, seizures, early neurological deterioration, cerebral edema, recurrent stroke, acute coronary syndrome, pulmonary thromboembolism, respiratory infection, urinary tract infection, sepsis, local hematoma or infection at the insertion site of the subcutaneous blood glucose monitor. Any other complication that is referred or detected during follow-up will also be recorded. | During follow-up period, up to 3 months | 
| Distribution of scores on the modified Rankin scale | Distribution of scores on the modified Rankin scale at 90 days (shift analysis). | At 90 days | 
| Mortality | Mortality at 3 months | At 3 months | 
| Presence of biomarkers of ischemia-reperfusion injury | Biomarkers of ischemia-reperfusion injury: miR-29b, miR-339, miR-15a, miR-100 and miR-424. Samples will be collected at the time of reperfusion and 24 hours later. | During reperfusion procedure and 24 hours later |