Clinical trial NCT05897554: 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
Overall status: RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Arterial Thrombosis
Posterior Circulation Brain Infarction
Keywords: Intra-arterial thrombolysis
Alteplase
Large vessel occlusion
Mechanical thrombectomy
Endovascular treatment
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Rate of modified Rankin Scale (mRS) score of 0-2
timeFrame: 90 days (±7 days) after randomization
Secondary outcomes:
measure: Change of eTICI
timeFrame: Before intra-arterial thrombolysis vs. immediately after the completion of intra-arterial thrombolysis
measure: Rate of mRS score of 0-3
timeFrame: 90 days (±7 days) after randomization
measure: Proportional distribution of modified Rankin Score
timeFrame: 90 days (±7 days) after randomization
measure: Improvement of the National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: 48 hours (±12 hours) after randomization
measure: Rate of early neurological improvement
timeFrame: 48 hours (±12 hours) after randomization
measure: Improvement of the NIHSS score
timeFrame: 7 days (±1 days) after randomization or discharge
measure: EQ-5D-5L
timeFrame: 90 days (±7 days) after randomization
measure: Barthel Index
timeFrame: 90 days (±7 days) after randomization
measure: All-cause mortality
timeFrame: 90 days (±7 days) after randomization
measure: Rate of symptomatic intracranial hemorrhage (sICH)
timeFrame: Within 48 hours after randomization
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Capital Medical University.
Study officials:
References: