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

Acute Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05897554
• Other study ID #: IAT-TOP
• Status: Recruiting
• Phase: N/A
• Start date: August 11, 2023
• Est. completion date: July 1, 2026

Study information

• Verified date: June 2023
• Source: Xuanwu Hospital, Beijing
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 376
• Est. completion date: July 1, 2026
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Arterial Thrombosis
• Brain Infarction
• Cerebral Infarction
• Infarction
• Ischemia
• Ischemic Stroke
• Posterior Circulation Brain Infarction
• Stroke
• Thrombosis

Intervention

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.

Locations

Country	Name	City	State
China	Xuanwu Hospital, Capital Medical University.	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Xuanwu Hospital, Beijing

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of modified Rankin Scale (mRS) score of 0-2	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Secondary	Change of eTICI	Change of eTICI after intra-arterial thrombolysis	Before intra-arterial thrombolysis vs. immediately after the completion of intra-arterial thrombolysis
Secondary	Rate of mRS score of 0-3	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Secondary	Proportional distribution of modified Rankin Score	The mRS score range from 0 (no disability) to 6 (death)	90 days (±7 days) after randomization
Secondary	Improvement of the National Institutes of Health Stroke Scale (NIHSS) score	The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)	48 hours (±12 hours) after randomization
Secondary	Rate of early neurological improvement	The NIHSS score 0-1 or decrease =8 from baseline NIHSS	48 hours (±12 hours) after randomization
Secondary	Improvement of the NIHSS score	The NIHSS score range from 0 (no deficit) to 42 (maximum deficit)	7 days (±1 days) after randomization or discharge
Secondary	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.	90 days (±7 days) after randomization
Secondary	Barthel Index	The Barthel Index range from 0 (severe disability) to 100 (no disability)	90 days (±7 days) after randomization
Secondary	All-cause mortality	Death defined as a mRS score of 6	90 days (±7 days) after randomization
Secondary	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.	Within 48 hours after randomization