Endovascular Stroke Treatment Only (ESTO) Trial
Endovascular Stroke Treatment Only (ESTO) Trial
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.
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.
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.