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

NCT05281549 | Unknown Phase 2 DMC

• 1 other identifier: PR-SMTJ-2019001F
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 28

Brief 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.

Conditions

Acute Ischemic Stroke

Keywords

TNK-tPA; rt-PA; Acute stroke; phase II trial

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• National Institutes of Health Stroke Scale (NIHSS)

  24±2 hours

• National Institutes of Health Stroke Scale (NIHSS)

  7±2days or discharge

• Modified Rankin Scale(mRS)

  90±7 days

• Modified Rankin Scale(mRS)

  90±7 days

• The new vascular events

  90±7 days

Other Outcomes (6)

• Symptomatic intracranial hemorrhage(sICH)

  24~30 hours post treatment

• Parenchymal hematoma type 2(PH2) intracranial hemorrhage

  24~30 hours post treatment

• Any intracranial hemorrhage

  24~30 hours post treatment

Study Arms (3)

Alteplase

ACTIVE COMPARATOR

Patients will receive intravenous Alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.

Drug: Alteplase

Tenecteplase 0.25mg/kg

EXPERIMENTAL

Patients will receive intravenous Tenecteplase, 0.25mg/kg, maximum 25mg, administered as a bolus over 5\~10 seconds

Drug: Tenecteplase

Tenecteplase 0.4mg/kg

EXPERIMENTAL

Patients will receive intravenous Tenecteplase, 0.4mg/kg, maximum 40mg, administered as a bolus over 5\~10 seconds

Drug: Tenecteplase

Interventions

Alteplase DRUG

Alteplase 0.9mg/kg are being used.

Also known as: rt-PA

Alteplase

Tenecteplase DRUG

Tenecteplase 0.25mg/kg are being used.

Also known as: TNK-tPA

Tenecteplase 0.25mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Jiangsu FENG HUA Biotech Pharmaceutical Co., Ltd: collaborator
• The Place Pharmaceutical(Jiangsu) Co., Ltd: collaborator

Study Sites (28)

Beijing Tiantan Hospital, Capital Medical University Beijing

Beijing, Beijing Municipality, 100000, China

Location

Quanzhou First Hospital

Quanzhou, Fujian, 362000, China

Location

Yue Bei People'S Hospital

Shaoguan, Guangdong, 512000, China

Location

Hengshui people's Hospital (Harrison International Peace Hospital)

Hengshui, Hebei, 053000, China

Location

Tangshan Gongren Hospital

Tangshan, Hebei, 063000, China

Location

Daqing Oilfield General Hospital

Daqing, Heilongjiang, 163000, China

Location

Baogang Hospital of Inner Monglia

Baotou, Inner Monglia, 014010, China

Location

Inner Mongolia Baotou Hospital

Baotou, Inner Mongolia, 014040, China

Location

Huai'an Second People's Hospital

Huai'an, Jiangsu, 121000, China

Location

The Affiliated Hospital of Xuzhou Meidcal University

Xuzhou, Jiangsu, 221006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Mei He Kou Central Hospital

Meihekou, Jilin, 135000, China

Location

Jilin Guowen Hospital

Siping, Jilin, 136100, China

Location

The First People's Hospital of Yinchuan

Yinchuan, Ningxia, 750001, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

Shandong Provincial Third Hospital

Jinan, Shandong, 250000, China

Location

Liaocheng People'S Hospital

Liaocheng, Shandong, 252006, China

Location

Linyi City People Hospital

Linyi, Shandong, 276000, China

Location

Qingdao Central Hospital

Qingdao, Shandong, 266000, China

Location

Yantai Yuhangding Hospital

Yantai, Shandong, 264000, China

Location

Shanghai Pudong Hospital

Shanghai, Shanghai Municipality, 201200, China

Location

Changzhi People'S Hospital

Changzhi, Shanxi, 046000, China

Location

The First People's Hospital of Jinzhong

Jinzhong, Shanxi, 030602, China

Location

First Hospital of Shanxi Medical University

Taiyuan, Shanxi, 030001, China

Location

Dazhu County People's Hospital

Dazhou, Sichuan, 635199, China

Location

Zigong First People'S Hospital

Zigong, Sichuan, 643000, China

Location

Zhejiang Provincial People'S Hospital

Hangzhou, Zhejiang, 310000, China

Location

Taizhou Hospital of Zhejiang Province

Taizhou, Zhejiang, 318000, China

Location

Related Publications (14)

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• 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, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater LA, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM; EXTEND-IA TNK Investigators. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018 Apr 26;378(17):1573-1582. doi: 10.1056/NEJMoa1716405.

  PMID: 29694815 RESULT

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

  RESULT

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

Tissue Plasminogen Activator; Tenecteplase; TNK-tissue plasminogen activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Study Officials

• Shuya Li

  IRB of Beijing Tiantan Hospital,Capital Medical University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Beijing Tiantan Hospital, Capital Medical University, Director of Neurology Center

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 16, 2022
• Study Start: May 2, 2021
• Primary Completion: January 28, 2022
• Study Completion: May 31, 2022
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (28)