Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients （3T Stroke-II）

Acute Ischemic Stroke Clinical Trial

Official title:

Thrombolysis Treated With TNK-tPA in Acute Ischemic Stroke Patients: a Multi-center, Block Randomized, Positive Drug Parallel Controlled Phase II Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05281549
• Other study ID #: PR-SMTJ-2019001F
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 2, 2021
• Est. completion date: May 31, 2022

Study information

• Verified date: March 2022
• Source: Beijing Tiantan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The trial is prospective, block randomized, open-label, blinded endpoint (PROBE) design. Patients with acute ischemic stroke, who are eligible for standard intravenous thrombolysis within 4.5 hours of stroke onset will be randomized 1:1:1 to 0.25mg/kg or 0.40mg/kg intravenous tenecteplase or 0.9 mg/kg alteplase before all participants undergo endovascular thrombectomy.

Description:

The study will be a multi-center, prospective, randomized, open- label, blinded endpoint (PROBE), controlled phase 2 trial (3 arm with 1:1:1 randomization) in ischemic stroke patients. Imagine is performed with CT or MRI acutely with imaging follow-up at 24-30 hours. The sample size is 225.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 225
• Est. completion date: May 31, 2022
• Est. primary completion date: January 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age =18 years old;

• The clinical diagnosis was Acute ischemic stroke The time from onset to treatment was < 4.5h; The time at which symptoms begin is defined as "the time at which they finally appear normal";

• mRS before onset was =1 points;

• Baseline NIHSS (at the time of randomization) should be > 5 and =25 points;

• Informed consent from the patient or surrogate.

Exclusion Criteria:

• Intracranial hemorrhage identified by CT or MRI (CMBs detected by SWI is not counted);

• Massive anterior cerebral infarction identified by CT or MRI (ASPECT < 6 or lesions larger than one third of the territory of the middle cerebral artery or with a volume larger than 70mL)

• A history of severe CNS damage (such as aneurysm or arteriovenous malformation, craniocerebral trauma, intracranial or spinal cord surgery)

• Onset with seizures, and the paralysis was suspected to be related to Todd paralysis.

• Administration of heparin within 48 hours preceding the onset of stroke with a baseline APTT exceeding the upper limit of the normal range.

• Oral anticoagulant (such as warfarin) treatment with baseline INR>1.7 or PT>15 s;

• Administration of thrombin inhibitors or factor Xa inhibitors within 48 hours preceding the onset of stroke with abnormal coagulation parameters or platelet count;

• BP couldn't be controlled with aggressive treatment. Uncontrolled hypertension was defined as systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, measured for three times every 10 minutes.

• Platelet count of less than 100×109/ L;

• Blood glucose <50 mg/dl (<2.8 mmol/L) or >400 mg/dl (22.22 mmol/L);

• History of intracranial hemorrhage or active hemorrhagic disease. (Such as gastrointestinal, urinary tract or retinal bleeding)

• Tumors with an increased risk of bleeding.

• Prolonged or traumatic cardiopulmonary resuscitation (>2 min), delivery within the last 10 days or recent puncture of non-compression vessels such as subclavian vein or jugular vein

• Acute pancreatitis or severe liver disease, including liver failure, cirrhosis, portal hypertension, esophageal varicose veins, and active hepatitis;

• Aortic arch dissection;

• Major surgery or severe trauma in the past 2 weeks;

• Subjects had serious, fatal, or disabling disease with an expected survival of less than 3 months;

• Unable to complete neurological assessment and follow-up visits because of dementia or mental illness;

• Pregnant women, lactating women, or have positive pregnancy test;

• Allergy to tenecteplase or alteplase or their components;

• Participation in other clinical trials within 3 months prior to screening;

• Unsuitable to involve in this study or would result in increased risk, as judged by the investigators.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Alteplase
Alteplase 0.9mg/kg are being used.
• Tenecteplase
Tenecteplase 0.25mg/kg are being used.
• Tenecteplase
Tenecteplase 0.4mg/kg are being used.

Locations

Country	Name	City	State
China	Baogang Hospital of Inner Monglia	Baotou	Inner Monglia
China	Inner Mongolia Baotou Hospital	Baotou	Inner Mongolia
China	Beijing Tiantan Hospital, Capital Medical University Beijing	Beijing	Beijing
China	The First Hospital of Jilin University	Changchun	Jilin
China	Changzhi People'S Hospital	Changzhi	Shanxi
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	Dazhu County People's Hospital	Dazhou	Sichuan
China	Zhejiang Provincial People'S Hospital	Hangzhou	Zhejiang
China	Hengshui people's Hospital (Harrison International Peace Hospital)	Hengshui	Hebei
China	Huai'an Second People's Hospital	Huai'an	Jiangsu
China	Shandong Provincial Third Hospital	Jinan	Shandong
China	The First People's Hospital of Jinzhong	Jinzhong	Shanxi
China	Liaocheng People'S Hospital	Liaocheng	Shandong
China	Linyi City People Hospital	Linyi	Shandong
China	Mei He Kou Central Hospital	Meihekou	Jilin
China	Qingdao Central Hospital	Qingdao	Shandong
China	Quanzhou First Hospital	Quanzhou	Fujian
China	Shanghai Pudong Hospital	Shanghai	Shanghai
China	Yue Bei People'S Hospital	Shaoguan	Guangdong
China	Jilin Guowen Hospital	Siping	Jilin
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Taizhou Hospital of Zhejiang Province	Taizhou	Zhejiang
China	Tangshan Gongren Hospital	Tangshan	Hebei
China	The Affiliated Hospital of Xuzhou Meidcal University	Xuzhou	Jiangsu
China	Yantai Yuhangding Hospital	Yantai	Shandong
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The First People's Hospital of Yinchuan	Yinchuan	Ningxia
China	Zigong First People'S Hospital	Zigong	Sichuan

Sponsors (3)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital	Jiangsu FENG HUA Biotech Pharmaceutical Co., Ltd, The Place Pharmaceutical(Jiangsu) Co., Ltd

Country where clinical trial is conducted

China, 

References & Publications (14)

Bandera E, Botteri M, Minelli C, Sutton A, Abrams KR, Latronico N. Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: a systematic review. Stroke. 2006 May;37(5):1334-9. Epub 2006 Mar 30. Review. — View Citation

Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Ba — View Citation

CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group. Lancet. 1997 Jun 7;349(9066):1641-9. — View Citation

Chinese Journal of Circulation, China Cardiovascular Disease Report 2015.

Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection of patients for trials of acute stroke therapy. Lancet Neurol. 2009 Mar;8(3):261-9. doi: 10.1016/S1474-4422(09)70041-9. Review. — View Citation

Guidelines Editing Group of Chinese Stroke Society, Guidelines for the Diagnosis and Treatment of High-risk Non-Disabling Ischemic Cerebrovascular Events, Chinese Journal of Stroke, June 2016, 11 (6), p481-491.

Haley EC Jr, Thompson JL, Grotta JC, Lyden PD, Hemmen TG, Brown DL, Fanale C, Libman R, Kwiatkowski TG, Llinas RH, Levine SR, Johnston KC, Buchsbaum R, Levy G, Levin B; Tenecteplase in Stroke Investigators. Phase IIB/III trial of tenecteplase in acute isc — View Citation

Hao Zilong, Liu Ming, Li Wei, et al. Stroke registration method and basic characteristics and functional outcomes of 3123 patients in Chengdu [J]. Chinese Journal of Neurology, 2011,12 (44) : 826-831.

Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, Ford I, Muir KW. Alteplase versus tenecteplase for thrombolysis after ischaemic stroke (ATTEST): a phase 2, randomised, open-label, blinded endpoint study. Lancet Neurol. 2015 Apr;14(4) — View Citation

Logallo N, Novotny V, Assmus J, Kvistad CE, Alteheld L, Rønning OM, Thommessen B, Amthor KF, Ihle-Hansen H, Kurz M, Tobro H, Kaur K, Stankiewicz M, Carlsson M, Morsund Å, Idicula T, Aamodt AH, Lund C, Næss H, Waje-Andreassen U, Thomassen L. Tenecteplase v — View Citation

Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, O'Brien B, Bladin C, McElduff P, Allen C, Bateman G, Donnan G, Davis S, Levi C. A randomized trial of tenecteplase versus alteplase for acute ischemic stroke. N Engl J Med. 2012 Mar 22;366(12): — View Citation

Standards and procedures for rapid reporting of safety data during drug clinical trials

Wang Z, Li J, Wang C, Yao X, Zhao X, Wang Y, Li H, Liu G, Wang A, Wang Y. Gender differences in 1-year clinical characteristics and outcomes after stroke: results from the China National Stroke Registry. PLoS One. 2013;8(2):e56459. doi: 10.1371/journal.po — View Citation

Wei JW, Heeley EL, Wang JG, Huang Y, Wong LK, Li Z, Heritier S, Arima H, Anderson CS; ChinaQUEST Investigators. Comparison of recovery patterns and prognostic indicators for ischemic and hemorrhagic stroke in China: the ChinaQUEST (QUality Evaluation of S — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Symptomatic intracranial hemorrhage(sICH)	Incidence of symptomatic intracranial hemorrhage (sICH) within 24~30 hours.( According to ECASSII)	24~30 hours post treatment
Other	Parenchymal hematoma type 2(PH2) intracranial hemorrhage	Incidence of intracranial hemorrhage (PH2) within 24~30 hours.	24~30 hours post treatment
Other	Any intracranial hemorrhage	Incidence of any intracranial hemorrhage within 24~30 hours.	24~30 hours post treatment
Other	Systematic bleeding	Incidence of Systematic bleeding within 30 hours. ( defined by PLATO)	30 hours
Other	Deaths	Mortality due to any cause at 90±7days.	90±7 days
Other	AEs/SAEs	Incidence of adverse events(AEs) / severe adverse events(SAEs) at 90±7 days.	90±7 days
Primary	Modified Rankin Scale(mRS)	Proportion of subjects with mRS scores of (0-1) at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)	90±7 days
Secondary	National Institutes of Health Stroke Scale (NIHSS)	NIHSS score at 24±2 hours.(Comments:The minimum and maximum values are from 0 to 40, and higher scores mean a worse outcome.)	24±2 hours
Secondary	National Institutes of Health Stroke Scale (NIHSS)	Proportion of subjects with = 4 point reduction in NIHSS or reaching 0-1 at 7 ± 2 days or before discharge (whichever occurs first).(Comments:The minimum and maximum values are from 0 to 40, and higher scores mean a worse outcome.)	7±2days or discharge
Secondary	Modified Rankin Scale(mRS)	Proportion of subjects with mRS scores of (0-2) at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)	90±7 days
Secondary	Modified Rankin Scale(mRS)	mRS scores at 90±7 days.(Comments:The minimum and maximum values are from 0 to 6,and higher scores mean a worse outcome.)	90±7 days
Secondary	The new vascular events	Incidence of the new vascular events, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardio-cerebral revascularization at 90±7 days. (including: carotid endarterectomy, intracranial and extracranial artery interventional therapy, intracranial and extracranial artery bypass surgery, coronary interventional or bypass therapy)	90±7 days
Secondary	Deaths	Vascular mortality at 90±7 days (mainly due to stroke, myocardial infarction or pulmonary embolism)	90±7 days
Secondary	EQ-5D	EQ-5D scores at 90±7 days.(Comments:The minimum and maximum values are from 0 to 100,and higher scores mean a better outcome.)	90±7 days