Clinical trial NCT06196320: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5
Official title: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5 Improving Neurological Functional Outcomes in Basilar Artery Occlusion With Tenecteplase in Extended Time Window: Multicentre, Prospective, Open-label, Blinded Endpoint (PROBE), Phase 3, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke, Acute
Keywords: rhTNK-tPA
rt-PA
Ischemic stroke
phase III trial
basilar artery occlusion
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2024-01-09
Enrollment: 452
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Modified Rankin Scale (mRS) 0-1 or return to baseline mRS
timeFrame: 3 months
Secondary outcomes:
measure: Modified Rankin Scale (mRS) 0-2 or return to baseline mRS
timeFrame: 3 months
measure: Modified Rankin Scale (mRS) 0-3 or return to baseline mRS
timeFrame: 3 months
measure: Ordinal analysis of the Modified Rankin Scale (mRS)
timeFrame: 3 months
measure: Early neurological improvement
timeFrame: 72 hours
measure: Successful reperfusion
timeFrame: initial DSA run prior to thrombectomy
measure: Symptomatic intracranial hemorrhage (sICH)
timeFrame: 36 hours
measure: All-cause mortality
timeFrame: 90 days
measure: Severe disability or death
timeFrame: 90 days
measure: Clinical deterioration
timeFrame: 24 hours
measure: Vessel recanalization
timeFrame: 24+/-6 hours
Other outcomes:
Locations:
city: Fuyang
country: China
facility: Taihe County Traditional Chinese Medicine Hospital
state: Anhui
city: Haozhou
country: China
facility: Lixin County People's Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Tian Tan Hospital, Capital Medical University
state: Beijing
city: Tianshui
country: China
facility: First People's Hospital of Tianshui
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Second Provincial General Hospital
state: Guangdong
city: Heyuan
country: China
facility: Heyuan People's Hospital
state: Guangdong
city: Huazhou
country: China
facility: Huazhou People's Hospital
state: Guangdong
city: Shaoguan
country: China
facility: Shaoguan Qujiang District People's Hospital
state: Guangdong
city: Guiyang
country: China
facility: The Second Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Guiyang
country: China
facility: The Second People's Hospital of Guiyang
state: Guizhou
city: Qiandongnan
country: China
facility: Qiandongnanzhou People's Hospital
state: Guizhou
city: Haikou
country: China
facility: Haikou People's Hospital
state: Hainan
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Handan
country: China
facility: Qiu County People's Hospital
state: Hebei
city: Qinhuangdao
country: China
facility: The Second Hospital of Qinhuangdao
state: Hebei
city: Tangshan
country: China
facility: Tangshan Guye Traditional Chinese Medicine Hospital
state: Hebei
city: Xingtai
country: China
facility: Qinghe County People's Hospital
state: Hebei
city: Harbin
country: China
facility: The 2nd Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Harbin
country: China
facility: The First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Shuangyashan
country: China
facility: Hongxinglong Hospital of Beidahuang Group
state: Heilongjiang
city: Anyang
country: China
facility: Huaxian People's Hospital of Henan
state: Henan
city: Jiaozuo
country: China
facility: Jiaozuo Coal Industry Central Hospital
state: Henan
city: Lingbao
country: China
facility: The First People Hospital of Lingbao
state: Henan
city: Liuyang
country: China
facility: Liuyang Jili Hospital
state: Henan
city: Nanyang
country: China
facility: Nanshi Hospital of Nanyang
state: Henan
city: Puyang
country: China
facility: Nanle County People's Hospital
state: Henan
city: Puyang
country: China
facility: Nanle Zhongxing Hospital
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Xinyang
country: China
facility: Guangshan County People's Hospital
state: Henan
city: Xinyang
country: China
facility: Xi County People's Hospital
state: Henan
city: Zhoukou
country: China
facility: Taikang Xian People's Hospital
state: Henan
city: Zhumadian
country: China
facility: People's Hospital of Queshan
state: Henan
city: Zhumadian
country: China
facility: Zhumadian Traditional Chinese Medicine Hospital
state: Henan
city: Chenzhou
country: China
facility: Chenzhou First People's Hospital
state: Hunan
city: Chenzhou
country: China
facility: The Fourth People's Hospital of Chenzhou
state: Hunan
city: Hengyang
country: China
facility: Hengyang Central Hospital
state: Hunan
city: Keshketeng Banner
country: China
facility: Keshketeng Banner Chinese-Mongolian Hospital
state: Inner Mongolia
city: Tongliao
country: China
facility: Tongliao People's Hospital
state: Inner Mongolia
city: Jiujiang
country: China
facility: Jiujiang First People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: Jilin Electric Power Hospital
state: Jilin
city: Siping
country: China
facility: Siping City Central People's Hospital
state: Jilin
city: Tonghua
country: China
facility: Liuhe County People's Hospital
state: Jilin
city: Jinzhou
country: China
facility: The First Affiliated Hospital of Jinzhou Medical University
state: Liaoning
city: Shenyang
country: China
facility: The People's Hospital of Liaoning Province
state: Liaoning
city: Dongying
country: China
facility: The Second People's Hospital of Dongying
state: Shandong
city: Gaomi
country: China
facility: Gaomi People's Hospital
state: Shandong
city: Laizhou
country: China
facility: Laizhou City People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Taian
country: China
facility: The Second Affiliated Hospital of Shandong First Medical University
state: Shandong
city: Weifang
country: China
facility: The Affiliated Hospital of Shandong Second Medical University
state: Shandong
city: Weifang
country: China
facility: Weifang People's Hospital
state: Shandong
city: Weihai
country: China
facility: Weihai Central Hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Taochun Central Hospital
state: Shandong
city: Zaozhuang
country: China
facility: Zaozhuang Municipal Hospital
state: Shandong
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo Beilun District People's Hospital
state: Zhejiang
city: Beijing
country: China
facility: Beijing Daxing District People's Hospital
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Melbourne
name: Bruce Campbell, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Melbourne
name: Fana Alemseged, MD, PhD
role: STUDY_DIRECTOR
affiliation: Beijing Tiantan Hospital
name: Yunyun Xiong, MD, PhD
role: STUDY_DIRECTOR
References: