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Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization (ANGEL-TNK)

Primary Purpose

Ischemic Stroke, Acute

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)
Best Medical Management
Sponsored by
Beijing Tiantan Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke, Acute

Eligibility Criteria

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

Inclusion Criteria: Clinical Inclusion Criteria: Age >18 years; NIHSS ≥2; Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW); Pre-stroke mRS score 0-1; Signed informed consent from patient or their health care proxy. Neuroimaging Inclusion Criteria: CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA; ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI; CT perfusion or MR perfusion: ischemic infarct core <70ml, mismatch ratio≥1.2, mismatch volume ≥15ml; Treated with MT resulting in an eTICI score 2b50-3 at end of the procedure. Patients with an eTICI score 2b50-3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study. Exclusion Criteria: Clinical Exclusion Criteria: IV thrombolysis used on admission; Contraindications to intravenous thrombolysis; Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h; IV heparin (heparinized saline allowed); Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test; Brain tumor (with mass effect); Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency Known coagulopathy, INR>1.7 or use of novel anticoagulants < 48h from symptom onset Platelets < 50*109/L; Suspicion of septic emboli or endocarditis Renal Failure as defined by a serum creatinine > 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate [GFR] < 30ml/min; Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason; Suspicion of aortic dissection; Parenchymal organ surgery and biopsy were performed in the past one month; Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month; History of life-threatening allergy (more than rash) to contrast medium; SBP >185 mmHg or DBP >110 mmHg refractory to treatment; Serious, advanced, terminal illness with anticipated life expectancy < 6 months; Participation in another randomized clinical trial that could confound the evaluation of the study; Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients (e.g. inability to understand and/or comply with study procedures and/or follow-up due to mental disorders, cognitive or mood disorders). Specific Neuroimaging Exclusion Criteria Midline shift or herniation, mass effect with effacement of the ventricles Evidence of acute intracranial hemorrhage on CT/MRI Acute bilateral strokes or multiple intracranial vessel occlusions Isolated extracranial ICA occlusion or tandem carotid / MCA occlusion Dissection of occluded artery on DSA after thrombectomy

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    TNK group

    control group

    Arm Description

    Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization

    Patients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization

    Outcomes

    Primary Outcome Measures

    Rate of excellent outcome
    Rate of 90 (±7) day modified Rankin scale (mRS) 0-1

    Secondary Outcome Measures

    Rate of sICH (Heidelberg Bleeding Classification)
    Rate of sICH (Heidelberg Bleeding Classification)
    Volume of Tmax>6s
    Infarct core volume change from baseline
    Infarct core volume change from baseline, assessed with NCCT at 7 days (±1 day) after randomization/at discharge or with MRI at 36 hours (±12 hours)
    mRS (shift analysis)
    mRS (shift analysis)
    Rate of good outcome
    Rate of mRS 0-2
    Rate of mRS 0-3
    Rate of mRS 0-3
    NIHSS 0-1 or decrease ≥10 from baseline NIHSS
    NIHSS 0-1 or decrease ≥10 from baseline NIHSS
    EQ-5D-5L score
    EQ-5D-5L score
    All-caused mortality
    All-caused mortality
    Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
    Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)

    Full Information

    First Posted
    November 14, 2022
    Last Updated
    November 24, 2022
    Sponsor
    Beijing Tiantan Hospital
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05624190
    Brief Title
    Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization
    Acronym
    ANGEL-TNK
    Official Title
    Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator rhTNK-tPA) Thrombolysis for Acute Large Vessel Occlusion After Successful Mechanical Thrombectomy Recanalization -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial (ANGEL-TNK)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 2022 (Anticipated)
    Primary Completion Date
    September 2023 (Anticipated)
    Study Completion Date
    December 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Beijing Tiantan Hospital

    4. Oversight

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

    5. Study Description

    Brief Summary
    The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Participants enrolled will be randomly assigned to study or control arm with a 1:1ratio. Study group will receive IA rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus best medical management, and control receive best medical management alone.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    Outcomes Assessor
    Allocation
    Randomized
    Enrollment
    256 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    TNK group
    Arm Type
    Experimental
    Arm Description
    Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization
    Arm Title
    control group
    Arm Type
    Active Comparator
    Arm Description
    Patients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization
    Intervention Type
    Drug
    Intervention Name(s)
    Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)
    Other Intervention Name(s)
    IA rhTNK-tPA
    Intervention Description
    The administration of rhTNK-tPA will be infused constant and slowly over 15min (0.125 mg/kg, Max 12.5mg) through a microcatheter.
    Intervention Type
    Other
    Intervention Name(s)
    Best Medical Management
    Intervention Description
    Best Medical Management
    Primary Outcome Measure Information:
    Title
    Rate of excellent outcome
    Description
    Rate of 90 (±7) day modified Rankin scale (mRS) 0-1
    Time Frame
    90±7 days after randomization
    Secondary Outcome Measure Information:
    Title
    Rate of sICH (Heidelberg Bleeding Classification)
    Description
    Rate of sICH (Heidelberg Bleeding Classification)
    Time Frame
    within 48 hours after randomization
    Title
    Volume of Tmax>6s
    Time Frame
    24 hours (±12 hours) after randomization
    Title
    Infarct core volume change from baseline
    Description
    Infarct core volume change from baseline, assessed with NCCT at 7 days (±1 day) after randomization/at discharge or with MRI at 36 hours (±12 hours)
    Time Frame
    7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization
    Title
    mRS (shift analysis)
    Description
    mRS (shift analysis)
    Time Frame
    90 days (±7 days) after randomization
    Title
    Rate of good outcome
    Description
    Rate of mRS 0-2
    Time Frame
    90 days (±7 days) after randomization
    Title
    Rate of mRS 0-3
    Description
    Rate of mRS 0-3
    Time Frame
    90 days (±7 days) after randomization
    Title
    NIHSS 0-1 or decrease ≥10 from baseline NIHSS
    Description
    NIHSS 0-1 or decrease ≥10 from baseline NIHSS
    Time Frame
    36 hours (±12hours) after randomization
    Title
    EQ-5D-5L score
    Description
    EQ-5D-5L score
    Time Frame
    90 days (±7 days) after randomization
    Title
    All-caused mortality
    Description
    All-caused mortality
    Time Frame
    90 days (±7 days) after randomization
    Title
    Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
    Description
    Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
    Time Frame
    within 48 hours after randomization

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Clinical Inclusion Criteria: Age >18 years; NIHSS ≥2; Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW); Pre-stroke mRS score 0-1; Signed informed consent from patient or their health care proxy. Neuroimaging Inclusion Criteria: CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA; ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI; CT perfusion or MR perfusion: ischemic infarct core <70ml, mismatch ratio≥1.2, mismatch volume ≥15ml; Treated with MT resulting in an eTICI score 2b50-3 at end of the procedure. Patients with an eTICI score 2b50-3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study. Exclusion Criteria: Clinical Exclusion Criteria: IV thrombolysis used on admission; Contraindications to intravenous thrombolysis; Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h; IV heparin (heparinized saline allowed); Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test; Brain tumor (with mass effect); Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency Known coagulopathy, INR>1.7 or use of novel anticoagulants < 48h from symptom onset Platelets < 50*109/L; Suspicion of septic emboli or endocarditis Renal Failure as defined by a serum creatinine > 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate [GFR] < 30ml/min; Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason; Suspicion of aortic dissection; Parenchymal organ surgery and biopsy were performed in the past one month; Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month; History of life-threatening allergy (more than rash) to contrast medium; SBP >185 mmHg or DBP >110 mmHg refractory to treatment; Serious, advanced, terminal illness with anticipated life expectancy < 6 months; Participation in another randomized clinical trial that could confound the evaluation of the study; Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients (e.g. inability to understand and/or comply with study procedures and/or follow-up due to mental disorders, cognitive or mood disorders). Specific Neuroimaging Exclusion Criteria Midline shift or herniation, mass effect with effacement of the ventricles Evidence of acute intracranial hemorrhage on CT/MRI Acute bilateral strokes or multiple intracranial vessel occlusions Isolated extracranial ICA occlusion or tandem carotid / MCA occlusion Dissection of occluded artery on DSA after thrombectomy
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Xiaochuan Huo, Dr.
    Phone
    +8613716292262
    Email
    huoxiaochuan@126.com

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes

    Learn more about this trial

    Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization

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