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

Sponsor

Xuanwu Hospital, Beijing (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05897554

Collaborator

(none)

376

Enrollment

Location

Arms

Anticipated Duration (Months)

10.4

Patients Per Site Per Month

Study Details

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 resulted in an increased likelihood of excellent neurological outcome at 90 days. However, CHOICE almost exclusively enrolled anterior circulation occlusions. Therefore, the clinical evidence of the efficacy and safety of post-endovascular reperfusion IAT in posterior circulation stroke is lacking.
There is a higher risk of ICH in the anterior circulation stroke than posterior circulation stroke. The investigators think IAT may be safer to be used in posterior circulation stroke. Also, there are more perforator artery in the posterior circulation, so IAT would be more likely to show its benefit. Therefore, the investigators would like to explore IA rt-PA for posterior circulation stroke after successful MT in our RCT.

Condition or Disease	Intervention/Treatment	Phase
Acute Ischemic Stroke Arterial Thrombosis Posterior Circulation Brain Infarction	Drug: intra-arterial alteplase	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

376 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Intra-arterial Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke Due to Large Vessel Occlusion in the Posterior Circulation (IAT-TOP)

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Successful mechanical thrombectomy plus intra-arterial alteplase group 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.	Drug: intra-arterial alteplase 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. Other Names: Intraarterial alteplase recombinant tissue plasminogen activator (r-tPA)
No Intervention: Successful mechanical thrombectomy only group 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.

Arm

Intervention/Treatment

Experimental: Successful mechanical thrombectomy plus intra-arterial alteplase group

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.

Drug: intra-arterial alteplase

Other Names:

Intraarterial alteplase recombinant tissue plasminogen activator (r-tPA)

No Intervention: Successful mechanical thrombectomy only group

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.

Outcome Measures

Primary Outcome Measures

Rate of modified Rankin Scale (mRS) score of 0-2 [90 days (±7 days) after randomization]
The mRS score range from 0 (no disability) to 6 (death)

Secondary Outcome Measures

Change of eTICI [Before intra-arterial thrombolysis vs. immediately after the completion of intra-arterial thrombolysis]
Change of eTICI after intra-arterial thrombolysis
Rate of mRS score of 0-3 [90 days (±7 days) after randomization]
The mRS score range from 0 (no disability) to 6 (death)
Proportional distribution of modified Rankin Score [90 days (±7 days) after randomization]
The mRS score range from 0 (no disability) to 6 (death)
Improvement of the National Institutes of Health Stroke Scale (NIHSS) score [48 hours (±12 hours) after randomization]
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
Rate of early neurological improvement [48 hours (±12 hours) after randomization]
The NIHSS score 0-1 or decrease ≥8 from baseline NIHSS
Improvement of the NIHSS score [7 days (±1 days) after randomization or discharge]
The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)
EQ-5D-5L [90 days (±7 days) after randomization]
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 [90 days (±7 days) after randomization]
The Barthel Index range from 0 (severe disability) to 100 (no disability)
All-cause mortality [90 days (±7 days) after randomization]
Death defined as a mRS score of 6
Rate of symptomatic intracranial hemorrhage (sICH) [48 hours (±12 hours) after randomization]
The sICH was defined based on modified SITS-MOST: local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h (-2/+12), or leading to death that the CEC/DSMB judges is causative of the deterioration.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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 substraction 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, lack 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