Endovascular Stroke Treatment Only (ESTO) Trial

Acute Ischemic Stroke Clinical Trial

Official title:

Endovascular Stroke Treatment Only (ESTO) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04240470
• Other study ID #: 2019141
• Status: Completed
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: October 23, 2021

Study information

• Verified date: December 2021
• Source: University of Missouri-Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The specific aims of this study are to:

1. Determine whether the endovascular treatment (mechanical thrombectomy) alone without using intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients demonstrates "promise" or a lack thereof ("futility") in deciding what would be the next phase III trial.

2. Determine the proportion of subjects with slight or no disability (a modified Rankin score (mRS) of 0-2) at 3 months after receiving endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA and compare with historical controls who were treated with IV rt-PA to identify (or lack of) futility.

3. Determine the proportion of subjects with improvement in the National Institutes of Health Stroke Scale (NIHSS) score of ≥8 points or achieving a score of 0-1 at 24 hours after the onset of stroke among subjects with acute ischemic stroke after receiving endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.

4. Determine the proportion of subjects with angiographic recanalization on post procedure angiogram according to modified Thrombolysis in Cerebral Infarction (TICI) perfusion flow categories among subjects with acute ischemic stroke after receiving endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.

5. Determine the proportion of subjects with treatment-related serious adverse events (SAEs) within 72 hours and development of symptomatic intracranial hemorrhage at 27 ±3hrs post treatment among subjects with acute ischemic stroke after receiving endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.

Description:

A phase II trial is proposed to address the question whether administration of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients who are candidates for endovascular treatment provides any additional value. The phase II trial will treat consecutive patients who are candidates for IV rt-PA and mechanical thrombectomy with just mechanical thrombectomy alone. Such trial will generate the necessary data for a definitive phase III trial. The trial is designed based on low rate of recanalization in patients with major arterial occlusion with IV rt-PA alone and no difference in rate of recanalization or distal embolization in patients who receive IV rt-PA and those who do not prior to mechanical thrombectomy. The rates of intracranial hemorrhage (ICH) and cost of hospitalization are higher when IV rt-PA is administered prior to mechanical thrombectomy. The trial will determine the proportion of patients with slight or no disability (a modified Rankin score (mRS) of 0-2) at 3 months after receiving endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA and compare with historical controls who were treated with IV rt-PA to determine futility.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 23, 2021
• Est. primary completion date: October 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• • Age: 18 through 90 years (i.e., candidates must have had their 18th birthday, but not had their 91st birthday).

• Symptom onset within 4.5 hours of onset of stroke symptoms. Time of onset is defined as the last time when the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep).

• An NIHSS = 6 at the time of evaluation. Thrombolysis in Cerebral Infarction (TICI) 0-1 flow in the intracranial internal carotid artery, M1 or M2 segment of the middle cerebral artery (MCA), or carotid terminus confirmed by Computed Tomography (CT) or magnetic resonance (MR) angiography that is accessible to the stent retriever or suction thrombectomy catheter.

• The procedure can be initiated according to guidelines of AHA/ASA which state that the treatment should be initiated (groin puncture) within 6 hours of symptom onset.

Exclusion Criteria:

• Clinical Exclusion Criteria

• History of stroke in the past 3 months.

• Previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or ruptured brain arteriovenous malformation.

• Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is normal.

• Severe hypertension at time of treatment; systolic blood pressure > 185 or diastolic > 110 mm Hg that cannot be corrected prior to treatment.

• Presumed septic embolus.

• Major surgery within the previous 14 days.

• Recent (within 90 days) severe head trauma or head trauma with loss of consciousness.

• Gastrointestinal malignancy or gastrointestinal hemorrhage within 21 days.

• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; or oral anticoagulant therapy with International Normalized Ratio (INR) > 1.7 or institutionally equivalent prothrombin time or platelets count <100,000 per microliter.

• Women of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission.

• Patients with renal failure that require hemodialysis or peritoneal dialysis.

• Low molecular weight heparins (such as Dalteparin, Enoxaparin, Tinzaparin, Fondaparinux) as deep vein thrombosis (DVT) prophylaxis or in full dose within the last 24 hours from screening unless anti-activated factor X (anti-factor Xa) assay less than 200% of control value.

• Patients who have received heparin within 48 hours must have a normal partial thromboplastin time (PTT) to be eligible.

• Patients who have received heparin or a direct thrombin inhibitor (Angiomax, Argatroban, Refludan) must have a normal PTT to be eligible.

• Patients on dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) may be considered after 48 hours after last intake of medication in patients with normal renal function (CrCl > 60 mL/minute). If moderate renal impairment, CrCl of 30-59 mL/minute, last dose should be 72 hours before procedure and 96 hours in severe renal impaired patients (CrCl of 15-29 mL/minute). The time interval between the last dose administration and the neurointerventional procedure appears to be the most reliable criterion for assessing the risk of bleeding events. Patients in whom time of last dose ingestion is unknown or within last 48 hours, can be included under following circumstances: normal PTT for dabigatran, normal prothrombin time for rivaroxaban, or anti-activated factor X (anti-factor Xa) assay rivaroxaban (Xarelto), apixaban (Eliquis), or edoxaban (Savaysa) less than 200% of control value.

• Subjects with an arterial puncture at a non-compressible site or a lumbar puncture in the previous 7 days.

• Patients with a seizure at onset of stroke.

• Patients with a pre-existing neurological or psychiatric disease that would confound the neurological or functional evaluations.

• Other serious, advanced, or terminal illness.

• Current participation in another research drug treatment protocol (patient cannot start another experimental agent until after 90 days).

Informed consent is not or cannot be obtained. For example, obtunded patients are not automatically excluded from the study. However, if the next of kin or legal guardian (i.e., the individual legally empowered in the state where the consent is obtained) cannot provide consent, randomization and entry into the study could not proceed.

CT Scan Exclusion Criteria

• High density lesion consistent with hemorrhage of any degree.

• Significant mass effect with midline shift.

• Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on the baseline CT scan or ASPECTS of < 4.

• Sulcal effacement and / or loss of grey-white differentiation alone are not contraindications for treatment.

CT Angiographic Exclusion Criteria

• Angiographic evidence of carotid dissection or complete cervical carotid occlusion.

• Arterial tortuosity, calcification, pre-existing stent, and/or stenosis, which would prevent the thrombectomy device from reaching the target vessel and/or preclude safe recovery of the endovascular devices.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemic Stroke
• Stroke

Intervention

Procedure:
• Thrombectomy
Participants will receive endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.

Locations

Country	Name	City	State
United States	University of Missouri	Columbia	Missouri

Sponsors (5)

Lead Sponsor	Collaborator
University of Missouri-Columbia	Eskisehir Osmangazi University Training and Research Hospital, Kartal Dr. Lütfi Kirdar City Hospital, Ondokuz Mayis University Training and Research Hospital, Sakarya University Training and Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Treatment-Related Serious Adverse Events	Assessement by the investigators for all patients	Within 72 hours of interventional treatment
Other	Symptomatic intracranial hemorrhage	Any hematoma within ischemic field with some mild space occupying effect but involving = 30% of the infarcted area, hematoma within ischemic field with space-occupying effect involving >30% of the infarcted area, any intraparenchymal hemorrhage remote from the ischemic field, subarachnoid hemorrhage, or intraventricular hemorrhage associated with a 4 points or more worsening on the NIHSS within 24 hrs	24 ± 3hrs post enrollment
Primary	Favorable Outcome	Modified Rankin Scale (mRS) score of 0-2: 0, No symptoms at all; 1, No significant disability despite symptoms; able to carry out all usual duties and activities; 2, Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. The modified Rankin Scale score ranges from 0, indicating no symptoms, to 6, indicating death.	90 days
Secondary	Angiographic Recanalization	Post procedure angiogram according to modified Thrombolysis in Cerebral Infarction perfusion flow categories: 0 = No perfusion. No antegrade flow beyond the point of occlusion.; = Perfusion past the initial obstruction but limited distal branch filling with little or slow distal perfusion; A = Perfusion of less than half of the vascular distribution of the occluded artery (eg, filling and perfusion through 1 M2 division); 2B = Perfusion of half or greater of the vascular distribution of the occluded artery (eg, filling and perfusion through 2 or more M2 divisions) 3 = Full perfusion with filling of all distal branches perfusion flow categories	Within 6 hours of interventional treatment
Secondary	Early Neurological Improvement	National Institutes of Health Stroke Scale (NIHSS) score of =8 points or achieving a score of 0-1 at 24 hours after the onset of stroke. NIHSS quantifies neurologic deficits in 11 categories. Level of consciousness, horizontal eye movement, visual fields, facial palsy, movement in each limb, sensation, language & speech, and extinction or inattention on one side of the body are tested. Scores range from 0 to 42, with 0 indicating normal function and higher scores indicating greater deficit severity.	24 hours post enrollment
Secondary	Quality of Life Status Using Standardized EQ-5D-3L (EuroQol Five Dimension, Three-Level) Questionnaire.	The EQ-5D-3L questionnaire consists of 5 questions in 5 different domains and allows for responses from 1 (the best outcome) to 3 (the worst outcome) in each of five categories (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Total scores range from 5 to 15, with lower scores indicating better quality of life and a higher score indicating a worse quality of life.	90 days
Secondary	Quality of Life Status Using EQ VAS (EuroQol Visual Analog Scale) Scores.	EuroQol outcome measurements is a printed 20 cm visual analogue scale (EQ VAS) that appears somewhat like a thermometer, on which a score from 0 (worst imaginable health state or death) to 100 (best imaginable health state) is marked by the patient (or, when necessary, their proxy) with the scale in view.	90 days