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

Not Applicable

Recruiting

• Conditions: Acute Ischemic Stroke; Posterior Circulation Brain Infarction; Arterial Thrombosis
• Interventions: Drug: intra-arterial alteplase

• Registration Number: NCT05897554
• Lead Sponsor: Xuanwu Hospital, Beijing

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.

In this study, one interim analysis will be performed when the enrollment volume reaches 50% of the total sample size (188 cases). DSMB will determine the premature termination or continuity of research.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-18
• Study First Submitted QC: 2023-06-08
• Study First Posted: 2023-06-09
• Study Start: 2023-08-11
• Status Verified: 2024-06
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22
• Primary Completion: 2025-07-01
• Study Completion: 2026-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 376

Inclusion Criteria

1. Symptoms and signs compatible with ischemia in the posterior circulation;
2. 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);
3. Age ≥18 years and ≤80 years;
4. Premorbid mRS ≤1;
5. National Institutes of Health Stroke Score (NIHSS) ≥6 at admission；
6. PC-ASPECTS on CT/CTA-Source Images/MRI-DWI 6-10；
7. Treated with endovascular thrombectomy (EVT) resulting in an eTICI score ≥2b50 at end of the procedure；
8. 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;
9. Informed consent obtained from the patient or his/her legal representative.

Exclusion Criteria

1. Contraindication to Intravenous Thrombolysis (except time to treatment);
2. Complete clinical recovery in the angiography suite by end of MT procedure;
3. More than 3 passes of thrombectomy device;
4. Dissection of occluded artery or intraoperative bleeding on DSA after thrombectomy;
5. 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;
6. Seizures at stroke onset which would preclude obtaining a baseline NIHSS;
7. Bilateral dilated pupils;
8. Severe contrast allergy or absolute contraindication to iodinated contrast;
9. Systolic pressure >185 mmHg or diastolic pressure >110 mmHg, and cannot be controlled by antihypertensive drugs;
10. Blood glucose <50 mg/dl (2.8 mmol/L) or >400 mg/dl (22.2 mmol/L);
11. Platelet <50*10^9/L, or aPTT >40 s, or PT >15 s;
12. 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;
13. 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;
14. Patients that cannot complete 90-day follow-up (e.g. no fixed residence, overseas patients, etc.);
15. Presumed vasculitis or septic embolization;
16. Suspicion of aortic dissection;
17. The patient has neurological disease or mental disorder before onset, which affects the assessment of the condition;
18. Females who are pregnant or in lactation;
19. Participating in other clinical trials that could confound the evaluation of the study;
20. Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Successful mechanical thrombectomy plus intra-arterial alteplase group	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 after intra-arterial thrombolysis.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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)
Rate of mRS score of 0-3	90 days (±7 days) after randomization	The mRS score range from 0 (no disability) to 6 (death)
All-cause mortality	90 days (±7 days) after randomization	Death defined as a mRS score of 6
Rate of symptomatic intracranial hemorrhage (sICH)	Within 48 hours after randomization	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.
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)
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)

Trial Locations

Locations (1)

Xuanwu Hospital, Capital Medical University.; 🇨🇳 Beijing, China