Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke

Phase 2

Completed

• Conditions: Stroke, Acute; Stroke, Ischemic
• Interventions: Drug: rhTNK-tPA; Other: Endovascular treatment

• Registration Number: NCT04733742
• Lead Sponsor: Xinqiao Hospital of Chongqing

Brief Summary

The purpose of this trial is to investigate whether intravenous rhTNK-tPA prior to endovascular treatment can improve 90-day functional outcome of stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of symptom onset.

Detailed Description

The DEVT, SKIP and DIRECT-MT trials showed that endovascular treatment alone is not inferior to intravenous alteplase bridging with endovascular treatment in terms of achieving 90-day functional independence for stroke patients with large vessel occlusion. The EXTEND-IA TNK part 1 and part 2 demonstrated that intravenous thrombolysis with tenecteplase is superior to alteplase before endovascular treatment. However, it is unclear whether intravenous tenecteplase bridging with endovascular treatment is superior to endovascular treatment alone. The purpose of this trial is to investigate whether intravenous rhTNK-tPA bridging with endovascular treatment is better than endovascular treatment alone for stroke patients with large vessel occlusion who are thrombolysis-eligible within 4.5 hours of onset.

Study Timeline

• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-01-31
• Study First Posted: 2021-02-02
• Study Start: 2022-05-09
• Primary Completion: 2024-12-16
• Study Completion: 2025-02-07
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-30
• Last Update Posted: 2025-04-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 550

Inclusion Criteria

1. Aged 18 years or older;
2. Patient with acute ischemic stroke who is eligible for intravenous thrombolysis treatment within 4.5 hours of time last known well;
3. No significant prestroke functional disability: for age <80 years, prestroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;
4. MCA-M1 or -M2, basilar artery, or posterior cerebral artery-P1 occlusion proved by CTA/MRA;
5. EVT is planned by clinical care team;
6. Written informed consent is obtained from patients and/or their legal representatives.

Exclusion Criteria

1. Intracranial hemorrhage on baseline CT or MR
2. Contraindication to intravenous thrombolytics
3. Already received intravenous thrombolytic after index stroke
4. Known pregnancy, or breastfeeding, or serum beta human chorionic gonadotropin test is positive on admission
5. Contraindication to radiographic contrast agents, nickel, titanium metals or their alloys
6. Current participation in another investigational drug clinical trial
7. Arterial tortuosity and/or other arterial disease that would lead to unstable access platform or prevent the thrombectomy device from reaching the target vessel
8. Patient with a preexisting neurological or psychiatric disease that would confound the outcome assessments
9. Patient with occlusions in two or more vascular territories (e.g. bilateral territories, or anterior and posterior circulation)
10. Mass effect or intracranial neoplasm on baseline CT or MR (except small meningioma)
11. Intracranial arteriovenous malformation or aneurysm on baseline CT or MR angiography
12. Any terminal disease with a life expectancy less than half a year
13. Unlikely to be available for follow-up at 90 days.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conbined treatment group	rhTNK-tPA	intravenous tenecteplase bridging with endovascular treatment
Conbined treatment group	Endovascular treatment	intravenous tenecteplase bridging with endovascular treatment
Endovascular treatment alone group	Endovascular treatment	endovascular treatment alone

Primary Outcome Measures

Name	Time	Method
Proportion of patients functionally independent (mRS score 0 to 2) at 90 days	90 days	functional independence

Secondary Outcome Measures

Name	Time	Method
Substantial reperfusion at initial angiogram	within 5 minutes at initial angiogram	evaluate effect of tenecteplase on reperfusion
Successful reperfusion at end-of-procedure angiography	15 minutes after initial angiogram	evaluate vascular patency after thrombectomy
First-pass reperfusion	After artery puncture, but before thrombectomy	defined as Expanded Treatment in Cerebral Infarction ≥2c after the first thrombectomy pass
Modified first-pass reperfusion	After artery puncture, but before thrombectomy	defined as Expanded Treatment in Cerebral Infarction ≥2b after the first thrombectomy pass
National Institutes of Health Stroke Scale (NIHSS) score	5 to 7 days or discharge	Neurological status
modified Rankin scale score	90 days	disability level
Proportion of patients non-disabled (mRS score 0 to 1) or return to pre-morbid mRS score at 90 days (for patients with mRS > 1)	90 days	excellent outcome
Proportion of patients ambulatory or bodily needs-capable or better (mRS score 0 to 3)	90 days	ambulatory or bodily needs-capable or better
Health-related quality of life, assessed with the European Quality Five Dimensions Five Level scale (EQ-5D-5L)	90 days	Health-related quality of life
Any radiologic intracranial hemorrhage within 48 hours	within 48 hours after endovascular treatment	evaluate intracranial hemorrhage
Symptomatic intracranial hemorrhage within 48 hours	within 48 hours after endovascular treatment	evaluate intracranial hemorrhage (Heidelberg classification)
Mortality within 90 days	90 days	evaluate death rate of the two treatment groups
Procedural-related complications	within 90 days	evaluate complications
Severe adverse events	within 90 days	evaluate any adverse events

Trial Locations

Locations (6)

Xinqiao Hospital of Army Medical University; 🇨🇳 Chongqing, Chongqing, China

The Second Hospital of Jiaozuo; 🇨🇳 Jiaozuo, Henan, China

Wuhan No. 1 Hospital; 🇨🇳 Wuhan, Hubei, China

The First Affiliated Hospital, Hengyang Medical School, University of South China; 🇨🇳 Hengyang, Hunan, China

Xiangtan Central Hospital; 🇨🇳 Xiangtan, Hunan, China

The 904th Hospital of CPLA; 🇨🇳 Wuxi, Jiangsu, China