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Endovascular Stroke Treatment And Reteplase Protocol ([ESTAR])

Primary Purpose

Ischemic Stroke

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Reteplase Injection
Sponsored by
Zeenat Qureshi Stroke Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 the onset of stroke symptoms. The 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 the beginning of sleep). An NIHSS ≥ 6 at the time of evaluation. (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 the guidelines of AHA/ASA which state that the treatment should be initiated (groin puncture) within 6 hours of symptom onset. 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 the initial CT scan is normal. Severe hypertension at the time of treatment; systolic blood pressure; 185 or diastolic; 110mm 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, and 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 the last intake of medication in patients with normal renal function (CrCl > 60 mL/minute). If moderate renal impairment, CrCl of 30-59 mL/minute, the last dose should be 72 hours before the 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 neuro-interventional procedure appears to be the most reliable criterion for assessing the risk of bleeding events. Patients in whom the time of last dose ingestion is unknown or within the last 48 hours, can be included under the 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 the 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 illnesses. 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 precluding safe recovery of the endovascular devices. The screening and recruitment of subjects All subjects presenting with acute stroke are currently evaluated by the stroke team, which consists of neurology residents, vascular neurology fellows, and the stroke attending. Study investigators will be notified by the stroke team members about potential patients, and the patients will be screened for eligibility by the investigators. If a patient meets the eligibility criteria, the patient or legally authorized representative will be approached for consent, depending on the patient's capability to make decisions. Patients/LARs will be informed of the option of standard treatment (IV rt-PA) -

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Arm Label

    IV thrombolysis

    IV reteplase (9 U bolus)

    IV reteplase (9 U bolus+9 U bolus)

    Arm Description

    Local institutional IV thrombolysis: IV alteplase (0.9 mg/kg) or IV Tenecteplase (TNK) (0.25 mg/kg) according to local institutional practice.

    Outcomes

    Primary Outcome Measures

    Angiographic recanalization
    Angiographic outcome will be evaluated based on post IV trial intervention CT angiogram or pre-thrombectomy angiogram and post procedure angiogram according to modified Thrombolysis in Cerebral Infarction (TICI) 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
    Early neurological improvement
    The proportion of patients with improvement in the NIHSS of ≥8 points or achieving a score of 0-1 at 3 days after the onset of stroke will be determined by comparing the NIHSS score at baseline and at 24 hours post enrollment.
    Symptomatic ICH at 27 ±3hrs post randomization:
    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.

    Secondary Outcome Measures

    Favorable outcome (defined as a mRS Scale score of 0-2) 90 days after ischemic stroke.
    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.

    Full Information

    First Posted
    May 28, 2023
    Last Updated
    May 28, 2023
    Sponsor
    Zeenat Qureshi Stroke Institute
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05900674
    Brief Title
    Endovascular Stroke Treatment And Reteplase Protocol
    Acronym
    [ESTAR]
    Official Title
    Endovascular Stroke Treatment And Reteplase Protocol
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2023 (Anticipated)
    Primary Completion Date
    July 2024 (Anticipated)
    Study Completion Date
    July 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Zeenat Qureshi Stroke Institute

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The proposed study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial involving patients with ischemic stroke who are candidates for receiving intravenous (IV) thrombolysis within 4.5 hours after stroke onset. The study aims to test the hypothesis that anterior circulation ischemic stroke patients, selected with "dual target" vessel occlusion within 4.5 hours of onset, will have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after IV reteplase, compared to IV alteplase. Patients will be randomized into one of three treatment arms: local institutional IV thrombolysis, IV reteplase (9 U bolus), or IV reteplase (9 U bolus + 9 U bolus). The study will assess the primary angiographic endpoint of partial or complete recanalization following administration of thrombolytics, as well as the time of recanalization and the time from symptom onset to recanalization. Additional outcome measures include early neurological improvement, assessed by a ≥4-point improvement in National Institutes of Health Stroke Scale (NIHSS) score in the first 24 hours compared to baseline. The trial will be conducted in three groups based on the site of baseline arterial occlusion: internal carotid artery (ICA), proximal middle cerebral artery (MCA - M1), or distal middle cerebral artery (MCA - M2). The study aims to evaluate third-generation thrombolytic - RETAVASE® (reteplase) and compare it to IV alteplase, in acute ischemic stroke patients.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ischemic Stroke

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    PROBE study (Prospective Randomized Open, Blinded End-point)
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    100 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    IV thrombolysis
    Arm Type
    Active Comparator
    Arm Description
    Local institutional IV thrombolysis: IV alteplase (0.9 mg/kg) or IV Tenecteplase (TNK) (0.25 mg/kg) according to local institutional practice.
    Arm Title
    IV reteplase (9 U bolus)
    Arm Type
    Experimental
    Arm Title
    IV reteplase (9 U bolus+9 U bolus)
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    Reteplase Injection
    Intervention Description
    To test the single dose of reteplase (9 U) and Maximum dose (18 U) in acute ischemic stroke patients.
    Primary Outcome Measure Information:
    Title
    Angiographic recanalization
    Description
    Angiographic outcome will be evaluated based on post IV trial intervention CT angiogram or pre-thrombectomy angiogram and post procedure angiogram according to modified Thrombolysis in Cerebral Infarction (TICI) 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
    Time Frame
    12 months
    Title
    Early neurological improvement
    Description
    The proportion of patients with improvement in the NIHSS of ≥8 points or achieving a score of 0-1 at 3 days after the onset of stroke will be determined by comparing the NIHSS score at baseline and at 24 hours post enrollment.
    Time Frame
    12 months
    Title
    Symptomatic ICH at 27 ±3hrs post randomization:
    Description
    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.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Favorable outcome (defined as a mRS Scale score of 0-2) 90 days after ischemic stroke.
    Description
    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.
    Time Frame
    12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    90 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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 the onset of stroke symptoms. The 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 the beginning of sleep). An NIHSS ≥ 6 at the time of evaluation. (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 the guidelines of AHA/ASA which state that the treatment should be initiated (groin puncture) within 6 hours of symptom onset. 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 the initial CT scan is normal. Severe hypertension at the time of treatment; systolic blood pressure; 185 or diastolic; 110mm 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, and 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 the last intake of medication in patients with normal renal function (CrCl > 60 mL/minute). If moderate renal impairment, CrCl of 30-59 mL/minute, the last dose should be 72 hours before the 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 neuro-interventional procedure appears to be the most reliable criterion for assessing the risk of bleeding events. Patients in whom the time of last dose ingestion is unknown or within the last 48 hours, can be included under the 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 the 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 illnesses. 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 precluding safe recovery of the endovascular devices. The screening and recruitment of subjects All subjects presenting with acute stroke are currently evaluated by the stroke team, which consists of neurology residents, vascular neurology fellows, and the stroke attending. Study investigators will be notified by the stroke team members about potential patients, and the patients will be screened for eligibility by the investigators. If a patient meets the eligibility criteria, the patient or legally authorized representative will be approached for consent, depending on the patient's capability to make decisions. Patients/LARs will be informed of the option of standard treatment (IV rt-PA) -
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Pashmeen Lakhani, M.B:B.S.
    Phone
    923196698353
    Email
    pashmeen.lakhani@zqsi.org
    First Name & Middle Initial & Last Name or Official Title & Degree
    Filza Sikandar, M.B:B.S.

    12. IPD Sharing Statement

    Learn more about this trial

    Endovascular Stroke Treatment And Reteplase Protocol

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