MedPath

Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5

Phase 3
Recruiting
Conditions
Ischemic Stroke, Acute
Interventions
Drug: Best Practice (which may include intravenous Alteplase)
Registration Number
NCT06196320
Lead Sponsor
Beijing Tiantan Hospital
Brief Summary

The trial is a multicentre, prospective, open-label, blinded endpoint (PROBE), phase 3, randomized controlled design. Patients with acute ischemic stroke due to basilar artery occlusion presenting within 24 hours will be randomized 1:1 to intravenous tenecteplase (0.25mg/kg, maximum 25mg) ± thrombectomy or 'best practice'which may be alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion.

Detailed Description

The study will be a multicentre, prospective, open-label, blinded endpoint (PROBE), randomized controlled trial (2 arm with 1:1 randomization) in patients with acute ischemic stroke due to basilar artery occlusion presenting to hospital within 24 hours of symptom onset.

Patients will be required to have complete or partial occlusion of the basilar artery on baseline computed tomography angiography (CTA)/magnetic resonance angiography (MRA), defined as 'potentially retrievable' thrombus in the basilar artery. Thrombectomy is permitted within 24 hours as part of standard care but is not mandatory.

Patients will be randomized to treatment with either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg within 4.5 hours from stroke onset) or intravenous tenecteplase (0.25mg/kg, maximum 25mg). Time of onset of symptoms is defined as described by the patient or witness; if unknown, it is considered to be the last time the patient was seen well. In patients presenting with mild (e.g. vertigo, dizziness, headache, diplopia, dysarthria) stuttering symptoms followed by sudden onset of clinical deterioration with decrease in conscious state or moderate to severe motor deficits, the time of deterioration in clinical state is taken as the estimated time of basilar artery occlusion.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
452
Inclusion Criteria
  1. Age ≥18.
  2. Patients presenting with posterior circulation ischemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
  3. Presence of a basilar artery occlusion, proven by CT Angiography. Basilar artery occlusion will be defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
  4. Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
  5. Local legal requirements for consent have been satisfied.
Exclusion Criteria
  1. Intracerebral haemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
  2. Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) on CT/ CTA-Source Images<6.
  3. Significant cerebellar mass effect or acute hydrocephalus.
  4. Established frank hypodensity on non-contrast CT indicating subacute infarction.
  5. Bilateral extensive brainstem ischemia.
  6. Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability).
  7. Other standard contraindications to intravenous thrombolysis.
  8. Contraindication to imaging with contrast agents.
  9. Clinically evident pregnant women.
  10. Vessel imaging showing both anterior and posterior circulation large vessel occlusion.
  11. Current participation in another research drug treatment protocol.
  12. Known terminal illness such that the patients would not be expected to survive a year.
  13. Planned withdrawal of care or comfort care measures.
  14. Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Best Practice (which may include intravenous Alteplase)Best Practice (which may include intravenous Alteplase)Intravenous alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion
TenecteplaseTenecteplaseIntravenous tenecteplase (0.25mg/kg, maximum 25mg) within 24 hours ± thrombectomy at treating clinician's discretion
Primary Outcome Measures
NameTimeMethod
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS3 months

The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).

Secondary Outcome Measures
NameTimeMethod
All-cause mortality90 days

All-cause mortality within 90 days.

Modified Rankin Scale (mRS) 0-3 or return to baseline mRS3 months

Proportion of patients with Modified Rankin Scale (mRS) 0-3 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).

Modified Rankin Scale (mRS) 0-2 or return to baseline mRS3 months

Proportion of patients with Modified Rankin Scale (mRS) 0-2 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).

Early neurological improvement72 hours

Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour National Institutes of Health Stroke Scale \[NIHSS\] score of ≥8 or 72 hour NIHSS 0-1).

Successful reperfusioninitial DSA run prior to thrombectomy

Proportion of patients with complete occlusion at baseline who achieve expanded Thrombolysis In Cerebral Infarction score (eTICI) 2b/3 on initial digital subtraction angiography (DSA) run prior to thrombectomy.

Severe disability or death90 days

Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death). Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).

Symptomatic intracranial hemorrhage (sICH)36 hours

Proportion of patients with Symptomatic intracranial hemorrhage (sICH) defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 hours of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.

Vessel recanalization24+/-6 hours

Vessel recanalization rate evaluated by CT or MR angiography within 24+/-6 hours (if performed).

Ordinal analysis of the Modified Rankin Scale (mRS)3 months

Ordinal analysis of the Modified Rankin Scale (mRS), merging category 5-6, at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).

Clinical deterioration24 hours

Proportion of patients with partially occlusive thrombus at baseline who have clinical deterioration within 24 hours leading to further treatment (e.g. endovascular thrombectomy).

Trial Locations

Locations (59)

Yantai Taochun Central Hospital

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Yantai, Shandong, China

Weihai Central Hospital

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Weihai, Shandong, China

Taihe County Traditional Chinese Medicine Hospital

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Fuyang, Anhui, China

Lixin County People's Hospital

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Haozhou, Anhui, China

First People's Hospital of Tianshui

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Tianshui, Gansu, China

Guangdong Second Provincial General Hospital

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Guangzhou, Guangdong, China

Heyuan People's Hospital

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Heyuan, Guangdong, China

Huazhou People's Hospital

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Huazhou, Guangdong, China

Shaoguan Qujiang District People's Hospital

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Shaoguan, Guangdong, China

The Second Affiliated Hospital of Guizhou Medical University

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Guiyang, Guizhou, China

The Second People's Hospital of Guiyang

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Guiyang, Guizhou, China

Qiandongnanzhou People's Hospital

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Qiandongnan, Guizhou, China

Haikou People's Hospital

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Haikou, Hainan, China

Affiliated Hospital of Hebei University

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Baoding, Hebei, China

Qiu County People's Hospital

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Handan, Hebei, China

The Second Hospital of Qinhuangdao

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Qinhuangdao, Hebei, China

Tangshan Guye Traditional Chinese Medicine Hospital

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Tangshan, Hebei, China

Qinghe County People's Hospital

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Xingtai, Hebei, China

The 2nd Affiliated Hospital of Harbin Medical University

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Harbin, Heilongjiang, China

The First Affiliated Hospital of Harbin Medical University

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Harbin, Heilongjiang, China

Hongxinglong Hospital of Beidahuang Group

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Shuangyashan, Heilongjiang, China

Huaxian People's Hospital of Henan

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Anyang, Henan, China

Jiaozuo Coal Industry Central Hospital

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Jiaozuo, Henan, China

The First People Hospital of Lingbao

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Lingbao, Henan, China

Liuyang Jili Hospital

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Liuyang, Henan, China

Nanshi Hospital of Nanyang

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Nanyang, Henan, China

Nanle County People's Hospital

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Puyang, Henan, China

Nanle Zhongxing Hospital

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Puyang, Henan, China

Puyang Oilfield General Hospital

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Puyang, Henan, China

Guangshan County People's Hospital

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Xinyang, Henan, China

Xi County People's Hospital

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Xinyang, Henan, China

Taikang Xian People's Hospital

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Zhoukou, Henan, China

People's Hospital of Queshan

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Zhumadian, Henan, China

Zhumadian Traditional Chinese Medicine Hospital

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Zhumadian, Henan, China

Chenzhou First People's Hospital

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Chenzhou, Hunan, China

The Fourth People's Hospital of Chenzhou

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Chenzhou, Hunan, China

Hengyang Central Hospital

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Hengyang, Hunan, China

Keshketeng Banner Chinese-Mongolian Hospital

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Keshketeng Banner, Inner Mongolia, China

Tongliao People's Hospital

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Tongliao, Inner Mongolia, China

Jiujiang First People's Hospital

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Jiujiang, Jiangxi, China

Jilin Electric Power Hospital

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Changchun, Jilin, China

Siping City Central People's Hospital

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Siping, Jilin, China

Liuhe County People's Hospital

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Tonghua, Jilin, China

The First Affiliated Hospital of Jinzhou Medical University

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Jinzhou, Liaoning, China

The People's Hospital of Liaoning Province

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Shenyang, Liaoning, China

The Second People's Hospital of Dongying

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Dongying, Shandong, China

Gaomi People's Hospital

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Gaomi, Shandong, China

Laizhou City People's Hospital

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Laizhou, Shandong, China

Linyi People's Hospital

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Linyi, Shandong, China

Qingdao Municipal Hospital

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Qingdao, Shandong, China

The Second Affiliated Hospital of Shandong First Medical University

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Taian, Shandong, China

The Affiliated Hospital of Shandong Second Medical University

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Weifang, Shandong, China

Weifang People's Hospital

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Weifang, Shandong, China

Zaozhuang Municipal Hospital

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Zaozhuang, Shandong, China

Linfen Central Hospital

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Linfen, Shanxi, China

The First Affiliated Hospital, Zhejiang University School of Medicine

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Hangzhou, Zhejiang, China

Ningbo Beilun District People's Hospital

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Ningbo, Zhejiang, China

Beijing Daxing District People's Hospital

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Beijing, China

Beijing Tian Tan Hospital, Capital Medical University

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Beijing, Beijing, China

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