- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04240470
Endovascular Stroke Treatment Only (ESTO) Trial
The specific aims of this study are to:
- 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.
- 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.
- 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.
- 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.
- 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.
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Missouri
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Columbia, Missouri, United States, 65212
- University of Missouri
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Thrombectomy
Participants will receive endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.
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Participants will receive endovascular treatment (mechanical thrombectomy) alone without using IV rt-PA.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Favorable Outcome
Time Frame: 90 days
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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.
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90 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Angiographic Recanalization
Time Frame: Within 6 hours of interventional treatment
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Post procedure angiogram according to modified Thrombolysis in Cerebral Infarction perfusion flow categories: 0 = No perfusion. No antegrade flow beyond the point of occlusion.
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
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Early Neurological Improvement
Time Frame: 24 hours post enrollment
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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.
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24 hours post enrollment
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Quality of Life Status Using Standardized EQ-5D-3L (EuroQol Five Dimension, Three-Level) Questionnaire.
Time Frame: 90 days
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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.
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90 days
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Quality of Life Status Using EQ VAS (EuroQol Visual Analog Scale) Scores.
Time Frame: 90 days
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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.
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90 days
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-Related Serious Adverse Events
Time Frame: Within 72 hours of interventional treatment
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Assessement by the investigators for all patients
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Within 72 hours of interventional treatment
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Symptomatic intracranial hemorrhage
Time Frame: 24 ± 3hrs post enrollment
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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
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24 ± 3hrs post enrollment
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Adnan Qureshi, University of Missouri-Columbia
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2019141
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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