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Intra-arterial Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP)

Primary Purpose

Acute Ischemic Stroke, Arterial Thrombosis, Posterior Circulation Brain Infarction

Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
intra-arterial alteplase
Sponsored by
Xuanwu Hospital, Beijing
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke focused on measuring Intra-arterial thrombolysis, Alteplase, Large vessel occlusion, Mechanical thrombectomy, Endovascular treatment

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Symptoms and signs compatible with ischemia in the posterior circulation; Basilar artery occlusion or vertebral artery occlusion without antegrade flow to the basilar artery confirmed by computed tomographic angiography (CTA)/ magnetic resonance angiography (MRA)/ digital subtraction angiography (DSA) Age ≥18 years and ≤80 years Premorbid mRS ≤1; National Institutes of Health Stroke Score (NIHSS) ≥6 at admission; PC-ASPECTS on CT/CTA-Source Images/MRI-DWI 6-10; Treated with endovascular thrombectomy (EVT) resulting in an eTICI score ≥2b50 at end of the procedure; Time from symptom onset to randomization<24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW) if symptoms are not witnessed or time of estimated basilar artery occlusion (defined as the time of sudden onset of basilar artery stroke symptoms, with no consideration of any preceding minor prodromal symptoms, as adjudicated by two neurologists) if symptoms are witnessed. Informed consent obtained from the patient or his/her legal representative; Exclusion Criteria: Contraindication to Intravenous Thrombolysis (except time to treatment); Complete clinical recovery in the angiography suite by end of MT procedure; More than 3 passes of thrombectomy device; Dissection of occluded artery or intraoperative bleeding on DSA after thrombectomy Patients in sedation and intubated patients could not be included if baseline NIHSS is not obtained by a neurologist or emergency physician prior to sedation or intubation. Seizures at stroke onset which would preclude obtaining a baseline NIHSS. Bilateral dilated pupils; Severe contrast allergy or absolute contraindication to iodinated contrast; Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs; Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L) Platelet <50*109/L, or aPTT >40 s, or PT >15 s; Known genetic or acquired bleeding diathesis, deficiency of anticoagulant factors, or oral anticoagulant drugs and INR > 1.7, or treated with direct oral anticoagulant agents in the prior 48 hours; Known Severe renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] <30, or patient requires hemodialysis or peritoneal dialysis; Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.); Presumed vasculitis or septic embolization; Suspicion of aortic dissection; The patient has neurological disease or mental disorder before onset, which affects the assessment of the condition; Females who are pregnant or in lactation; Participating in other clinical trials 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

Sites / Locations

  • Xuanwu Hospital, Capital Medical University.Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Successful mechanical thrombectomy plus intra-arterial alteplase group

Successful mechanical thrombectomy only group

Arm Description

For patients in the successful MT plus intra-arterial alteplase group, after successful recanalization, neurointerventionalists administered intra-arterial thrombolysis with alteplase according to protocol. The angiographic scores will be assessed after intra-arterial thrombolysis.

For patients in the successful MT only group, the choice of MT strategy will be made by the qualified neurointerventionalist, including stent retriever, aspiration and a combination technology. Patients who underwent more than 3 thrombectomy procedures were excluded from the study. Rescue therapy was performed at the discretion of the neurointerventionalist in case of the grade of stenosis at the occlusion site was presented to be more than 70% after MT.

Outcomes

Primary Outcome Measures

Rate of modified Rankin Scale (mRS) score of 0-2
The mRS score range from 0 (no disability) to 6 (death)

Secondary Outcome Measures

Change of eTICI
Change of eTICI after intra-arterial thrombolysis
Rate of mRS score of 0-3
The mRS score range from 0 (no disability) to 6 (death)
Proportional distribution of modified Rankin Score
The mRS score range from 0 (no disability) to 6 (death)
Improvement of the National Institutes of Health Stroke Scale (NIHSS) score
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
Rate of early neurological improvement
The NIHSS score 0-1 or decrease ≥8 from baseline NIHSS
Improvement of the NIHSS score
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
EQ-5D-5L
The EQ-5D 5-Levels (EQ-5D-5L) range from 5 (no problems) to 25 (extreme problems), which deceased patients have a utility of 0.
Barthel Index
The Barthel Index range from 0 (severe disability) to 100 (no disability)
All-cause mortality
Death defined as a mRS score of 6
Rate of symptomatic intracranial hemorrhage (sICH)
The sICH was assessed based on the Heidelberg Bleeding Classification, defined as 1) ≥4 points total NIHSS at the time of diagnosis compared to immediately before worsening; 2) ≥2 point in one NIHSS category. The rationale for this is to capture new hemorrhages that produce new neurological symptoms, making them clearly symptomatic but not causing worsening in the original stroke territory; 3) Leading to intubation/hemicraniectomy/EVD placement or other major medical/surgical intervention; 4) Absence of alternative explanation for deterioration.

Full Information

First Posted
May 18, 2023
Last Updated
September 7, 2023
Sponsor
Xuanwu Hospital, Beijing
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1. Study Identification

Unique Protocol Identification Number
NCT05897554
Brief Title
Intra-arterial Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP)
Official Title
Intra-arterial Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke Due to Large Vessel Occlusion in the Posterior Circulation (IAT-TOP)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 11, 2023 (Actual)
Primary Completion Date
July 1, 2025 (Anticipated)
Study Completion Date
July 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xuanwu Hospital, Beijing

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The CHOICE study suggested that the use of adjunct intra-arterial alteplase after successful endovascular reperfusion in large vessel occlusion acute ischemic strokes may result in a greater likelihood of excellent neurological outcome at 90 days. However, CHOICE was a phase-2 trial and almost exclusively enrolled anterior circulation occlusions. Therefore, data on the safety and efficacy of post-endovascular reperfusion IAT in posterior circulation stroke is lacking. In general, anterior circulation strokes are associated with a higher risk of ICH than posterior circulation strokes. Therefore, we believe it might be safer to perform post-endovascular reperfusion IAT posterior circulation stroke. Also, there are more perforator artery in the posterior circulation, IAT would be more likely to show its benefit. Therefore, we would like to explore IA rt-PA for posterior circulation stroke after successful MT in our RCT.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Ischemic Stroke, Arterial Thrombosis, Posterior Circulation Brain Infarction
Keywords
Intra-arterial thrombolysis, Alteplase, Large vessel occlusion, Mechanical thrombectomy, Endovascular treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
376 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Successful mechanical thrombectomy plus intra-arterial alteplase group
Arm Type
Experimental
Arm Description
For patients in the successful MT plus intra-arterial alteplase group, after successful recanalization, neurointerventionalists administered intra-arterial thrombolysis with alteplase according to protocol. The angiographic scores will be assessed after intra-arterial thrombolysis.
Arm Title
Successful mechanical thrombectomy only group
Arm Type
No Intervention
Arm Description
For patients in the successful MT only group, the choice of MT strategy will be made by the qualified neurointerventionalist, including stent retriever, aspiration and a combination technology. Patients who underwent more than 3 thrombectomy procedures were excluded from the study. Rescue therapy was performed at the discretion of the neurointerventionalist in case of the grade of stenosis at the occlusion site was presented to be more than 70% after MT.
Intervention Type
Drug
Intervention Name(s)
intra-arterial alteplase
Other Intervention Name(s)
Intraarterial alteplase recombinant tissue plasminogen activator (r-tPA)
Intervention Description
For patients in the successful MT plus intra-arterial alteplase group, after successful recanalization, neurointerventionalists administered intra-arterial thrombolysis with alteplase according to protocol. The angiographic scores will be assessed immediately after intra-arterial thrombolysis.
Primary Outcome Measure Information:
Title
Rate of modified Rankin Scale (mRS) score of 0-2
Description
The mRS score range from 0 (no disability) to 6 (death)
Time Frame
90 days (±7 days) after randomization
Secondary Outcome Measure Information:
Title
Change of eTICI
Description
Change of eTICI after intra-arterial thrombolysis
Time Frame
Before intra-arterial thrombolysis vs. immediately after the completion of intra-arterial thrombolysis
Title
Rate of mRS score of 0-3
Description
The mRS score range from 0 (no disability) to 6 (death)
Time Frame
90 days (±7 days) after randomization
Title
Proportional distribution of modified Rankin Score
Description
The mRS score range from 0 (no disability) to 6 (death)
Time Frame
90 days (±7 days) after randomization
Title
Improvement of the National Institutes of Health Stroke Scale (NIHSS) score
Description
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
Time Frame
48 hours (±12 hours) after randomization
Title
Rate of early neurological improvement
Description
The NIHSS score 0-1 or decrease ≥8 from baseline NIHSS
Time Frame
48 hours (±12 hours) after randomization
Title
Improvement of the NIHSS score
Description
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
Time Frame
7 days (±1 days) after randomization or discharge
Title
EQ-5D-5L
Description
The EQ-5D 5-Levels (EQ-5D-5L) range from 5 (no problems) to 25 (extreme problems), which deceased patients have a utility of 0.
Time Frame
90 days (±7 days) after randomization
Title
Barthel Index
Description
The Barthel Index range from 0 (severe disability) to 100 (no disability)
Time Frame
90 days (±7 days) after randomization
Title
All-cause mortality
Description
Death defined as a mRS score of 6
Time Frame
90 days (±7 days) after randomization
Title
Rate of symptomatic intracranial hemorrhage (sICH)
Description
The sICH was assessed based on the Heidelberg Bleeding Classification, defined as 1) ≥4 points total NIHSS at the time of diagnosis compared to immediately before worsening; 2) ≥2 point in one NIHSS category. The rationale for this is to capture new hemorrhages that produce new neurological symptoms, making them clearly symptomatic but not causing worsening in the original stroke territory; 3) Leading to intubation/hemicraniectomy/EVD placement or other major medical/surgical intervention; 4) Absence of alternative explanation for deterioration.
Time Frame
Within 48 hours after randomization

10. Eligibility

Sex
All
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Symptoms and signs compatible with ischemia in the posterior circulation; Basilar artery occlusion or vertebral artery occlusion without antegrade flow to the basilar artery confirmed by computed tomographic angiography (CTA)/ magnetic resonance angiography (MRA)/ digital subtraction angiography (DSA) Age ≥18 years and ≤80 years Premorbid mRS ≤1; National Institutes of Health Stroke Score (NIHSS) ≥6 at admission; PC-ASPECTS on CT/CTA-Source Images/MRI-DWI 6-10; Treated with endovascular thrombectomy (EVT) resulting in an eTICI score ≥2b50 at end of the procedure; Time from symptom onset to randomization<24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW) if symptoms are not witnessed or time of estimated basilar artery occlusion (defined as the time of sudden onset of basilar artery stroke symptoms, with no consideration of any preceding minor prodromal symptoms, as adjudicated by two neurologists) if symptoms are witnessed. Informed consent obtained from the patient or his/her legal representative; Exclusion Criteria: Contraindication to Intravenous Thrombolysis (except time to treatment); Complete clinical recovery in the angiography suite by end of MT procedure; More than 3 passes of thrombectomy device; Dissection of occluded artery or intraoperative bleeding on DSA after thrombectomy Patients in sedation and intubated patients could not be included if baseline NIHSS is not obtained by a neurologist or emergency physician prior to sedation or intubation. Seizures at stroke onset which would preclude obtaining a baseline NIHSS. Bilateral dilated pupils; Severe contrast allergy or absolute contraindication to iodinated contrast; Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs; Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L) Platelet <50*109/L, or aPTT >40 s, or PT >15 s; Known genetic or acquired bleeding diathesis, deficiency of anticoagulant factors, or oral anticoagulant drugs and INR > 1.7, or treated with direct oral anticoagulant agents in the prior 48 hours; Known Severe renal Failure as defined by a serum creatinine > 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate [GFR] <30, or patient requires hemodialysis or peritoneal dialysis; Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.); Presumed vasculitis or septic embolization; Suspicion of aortic dissection; The patient has neurological disease or mental disorder before onset, which affects the assessment of the condition; Females who are pregnant or in lactation; Participating in other clinical trials 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
Facility Information:
Facility Name
Xuanwu Hospital, Capital Medical University.
City
Beijing
ZIP/Postal Code
100053
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liqun Jiao, Dr.
Phone
13911224991
Email
liqunjiao@sina.cn

12. IPD Sharing Statement

Learn more about this trial

Intra-arterial Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP)

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