Ignite Creation Date:
2025-12-25 @ 3:22 AM
Ignite Modification Date:
2026-01-01 @ 4:32 AM
Study NCT ID:
NCT06987305
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-05-23
First Post:
2025-05-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Intravenous rhTNK-tPA Before Stroke Thrombectomy in the Extended Time Window
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000083242', 'term': 'Ischemic Stroke'}], 'ancestors': [{'id': 'D020521', 'term': 'Stroke'}, {'id': 'D002561', 'term': 'Cerebrovascular Disorders'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 820}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-10-01', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2029-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-05-22', 'studyFirstSubmitDate': '2025-05-07', 'studyFirstSubmitQcDate': '2025-05-22', 'lastUpdatePostDateStruct': {'date': '2025-05-23', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-05-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-10-01', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Proportion of patients functionally independent (mRS score 0 to 2) at 90 days', 'timeFrame': '90 days post-randomization', 'description': 'functional independence'}], 'secondaryOutcomes': [{'measure': 'Substantial reperfusion (defined as an eTICI grade of 2b, 2c, or 3) at initial angiogram', 'timeFrame': 'within 5 minutes at initial angiogram', 'description': 'The expanded Thrombolysis In Cerebral Infarction (eTICI) reperfusion grading system is a 6-point scale: 0 indicates no reperfusion noted; 1, reduction in thrombus without filling of distal arterial branches; 2a, reperfusion of \\<50% of the territory; 2b, a reperfusion of ≥50% of the territory; 2c, near-complete perfusion with distal slow flow or presence of small cortical emboli; and 3, complete reperfusion. Successful reperfusion at initial angiogram prior to thrombectomy was defined as an eTICI grade of 2b, 2c, or 3 on the first intracranial angiogram.'}, {'measure': 'Successful reperfusion (defined as an eTICI grade of 2b, 2c, or 3) at end-of-procedure angiography', 'timeFrame': '15 minutes after initial angiogram', 'description': 'The expanded Thrombolysis In Cerebral Infarction (eTICI) reperfusion grading system is a 6-point scale: 0 indicates no reperfusion noted; 1, reduction in thrombus without filling of distal arterial branches; 2a, reperfusion of \\<50% of the territory; 2b, a reperfusion of ≥50% of the territory; 2c, near-complete perfusion with distal slow flow or presence of small cortical emboli; and 3, complete reperfusion. This outcome will be evaluate at the end of procedure.'}, {'measure': 'Modified first-pass reperfusion', 'timeFrame': 'Perioperative (After artery puncture, but the start of procedure)', 'description': 'defined as Expanded Treatment in Cerebral Infarction 2b, 2c, or 3 after the first thrombectomy pass'}, {'measure': 'First-pass reperfusion', 'timeFrame': 'Perioperative (After artery puncture, but the start of procedure)', 'description': 'defined as Expanded Treatment in Cerebral Infarction 2c, or 3 after the first thrombectomy pass'}, {'measure': 'Final infarct volume on day 1.5 MRI/CT', 'timeFrame': '1.5 days post-randomization', 'description': 'Infarct volume quantified via MRI/CT , with manual correction by certified radiologists.'}, {'measure': 'Symptomatic intracranial hemorrhage within 48 hours', 'timeFrame': 'within 48 hours after endovascular treatment', 'description': 'evaluate intracranial hemorrhage (Heidelberg classification)'}, {'measure': 'Mortality within 90 days', 'timeFrame': '90 days post-randomization', 'description': 'evaluate death rate of the two treatment groups'}, {'measure': 'Procedural-related complications', 'timeFrame': 'within 90 days', 'description': 'evaluate complications'}, {'measure': 'Severe adverse events', 'timeFrame': 'within 90 days', 'description': 'evaluate any adverse events'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['acute ischemic stroke', 'endovascular treatment', 'rhTNK-tPA'], 'conditions': ['Stroke, Acute Ischemic']}, 'referencesModule': {'references': [{'pmid': '38329148', 'type': 'BACKGROUND', 'citation': 'Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, Sangha N, Kim M, Froehler MT, Schwartz NE, Clark WM, Kircher CE, Yang M, Massaro L, Lu XY, Rippon GA, Broderick JP, Butcher K, Lansberg MG, Liebeskind DS, Nouh A, Schwamm LH, Campbell BCV; TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. N Engl J Med. 2024 Feb 22;390(8):701-711. doi: 10.1056/NEJMoa2310392. Epub 2024 Feb 8.'}, {'pmid': '39654273', 'type': 'BACKGROUND', 'citation': "Yogendrakumar V, Campbell BC, Churilov L, Garcia-Esperon C, Choi PM, Cordato DJ, Guha P, Sharma G, Chen C, McDonald A, Thijs V, Mamun A, Dos Santos A, Balabanski AH, Kleinig TJ, Butcher KS, Devlin MJ, O'Rourke F, Donnan GA, Davis SM, Levi CR, Ma H, Parsons MW. Extending the time window for tenecteplase by effective reperfusion of penumbral tissue in patients with large vessel occlusion: Rationale and design of a multicenter, prospective, randomized, open-label, blinded-endpoint, controlled phase 3 trial. Int J Stroke. 2025 Mar;20(3):367-372. doi: 10.1177/17474930241308660. Epub 2024 Dec 31."}]}, 'descriptionModule': {'briefSummary': 'This randomized, double-blind, placebo-controlled phase III clinical trial aims to evaluate the efficacy and safety of intravenous recombinant human tenecteplase (rhTNK-tPA) in acute ischemic stroke patients with large vessel occlusion presenting 4.5-24 hours after last known well. The study will address two primary questions: 1) Whether rhTNK-tPA enhances pre-thrombectomy reperfusion rates and improves 90-day functional outcomes compared to placebo; 2) Whether rhTNK-tPA increases the risk of symptomatic intracranial hemorrhage and mortality.\n\nParticipants will be randomized to receive either a single bolus of rhTNK-tPA (0.25 mg/kg, max 25 mg) or matching placebo administered intravenously over 5 seconds. Key assessments include repeat neuroimaging (CT/CTA or MRI/MRA) at 24 hours post-treatment to evaluate reperfusion, NIH Stroke Scale score at day 5-7, and modified Rankin Scale score assessment at 90 days. Safety monitoring will focus on hemorrhagic transformation and mortality events throughout the study period.', 'detailedDescription': 'This multicenter, phase III trial employs a randomized, double-blind, placebo-controlled design to investigate the therapeutic window extension for rhTNK-tPA in large vessel occlusion stroke. Eligible participants are adults with large vessel occlusion confirmed by vascular imaging (CTA/MRA), and salvageable brain tissue demonstrated by perfusion imaging (CTP/MRP) mismatch. Exclusion criteria include contraindications to thrombolysis, and large core infarction (\\>70 mL on CTP).\n\nPatients will be randomized 1:1 to receive either weight-adjusted rhTNK-tPA (0.25 mg/kg) or placebo. All participants will undergo endovascular thrombectomy.\n\nThe primary outcome is functional independence (mRS 0-2) at 90 days. Secondary outcomes include substantial reperfusion at initial angiogram, first-pass reperfusion, final infarct volume on day 1.5 MRI/CT, etc. Safety outcomes include symptomatic intracranial hemorrhage per Heidelberg Bleeding Classification criteria within 36 hours, and 90-day mortality.\n\nSafety monitoring includes independent adjudication of hemorrhagic events and all-cause mortality. A sample size of 820 participants provides 80% power to detect a 10% absolute difference in functional independence (α=0.05).\n\nThe trial incorporates centralized blinded outcome assessment and intention-to-treat analysis, with data oversight by an independent clinical events committee and data safety monitoring board.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Age ≥18 years;\n2. Acute ischemic stroke presenting within 4.5-24 hours of last known well;\n3. No significant pre-stroke functional disability: for age \\<80 years, pre-stroke modified Rankin scale (mRS) ≤2; for age ≥80 years, prestroke mRS ≤1;\n4. Baseline NIHSS score ≥5;\n5. Imaging criteria of BOTH:\n\n 1. Occlusion on CTA/MRA in one of the following vessels: M1/M2 segment of middle cerebral artery, A1 segment of anterior cerebral artery, V4 segment of vertebral artery, basilar artery, or P1 segment of posterior cerebral artery. For A1, or P1 occlusions, vessel diameter must be ≥0.75 mm;\n 2. For anterior circulation occlusion: CTP/MRP demonstrating mismatch ratio ≥1.8, absolute mismatch volume ≥15 mL, and ischemic core volume \\<70 mL; OR have a mismatch between the presence of an abnormal signal on MRI diffusion-weighted imaging and no visible signal change on FLAIR. For posterior circulation occlusion: pc-ASPECTS score ≥6.\n6. Plan to received endovascular thrombectomy;\n7. The patient or their legal representative provides written informed consent.\n\nExclusion Criteria:\n\n1. Intracranial hemorrhage confirmed by CT/MRI;\n2. Already received intravenous thrombolytic after index stroke.;\n3. Pregnancy or lactation;\n4. Concurrent participation in other investigation drug clinical trials;\n5. Arterial tortuosity or other vascular anomalies precluding endovascular access to target vessel;\n6. Pre-existing neurological/psychiatric disorders interfering with neurological assessment;\n7. Space-occupying intracranial tumors (except small meningiomas ≤3 cm);\n8. Intracranial aneurysm or arteriovenous malformation;\n9. Terminal illness with life expectancy \\<6 months;\n10. Anticipated inability to complete follow-up assessments.'}, 'identificationModule': {'nctId': 'NCT06987305', 'briefTitle': 'Intravenous rhTNK-tPA Before Stroke Thrombectomy in the Extended Time Window', 'organization': {'class': 'OTHER', 'fullName': 'Xinqiao Hospital of Chongqing'}, 'officialTitle': 'Intravenous rhTNK-tPA Versus Placebo Before Endovascular Thrombectomy For Stroke Patient With Large Vessel Occlusion In The Extended Time Window: the BRIDGE-TNK EXTEND Randomized, Placebo-controlled, Double-blind Trial', 'orgStudyIdInfo': {'id': 'BRIDGE-TNK EXTEND'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'rhTNK-tPA group', 'description': 'Patients in this group will be treated with intravenous rhTNK-tPA and endovascular thrombectomy', 'interventionNames': ['Drug: Intravenous rhTNK-tPA', 'Procedure: Endovascular thrombectomy']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo group', 'description': 'Patients in this group will be treated with intravenous placebo and endovascular thrombectomy', 'interventionNames': ['Drug: Intravenous placebo', 'Procedure: Endovascular thrombectomy']}], 'interventions': [{'name': 'Intravenous rhTNK-tPA', 'type': 'DRUG', 'otherNames': ['Intravenous tenecteplase', 'Intravenous TNK'], 'description': 'Patients will received intravenous rhTNK-tPA', 'armGroupLabels': ['rhTNK-tPA group']}, {'name': 'Intravenous placebo', 'type': 'DRUG', 'otherNames': ['Intravenous placebo (a look-alike substance that contains no drug)'], 'description': 'Patients will received intravenous placebo', 'armGroupLabels': ['Placebo group']}, {'name': 'Endovascular thrombectomy', 'type': 'PROCEDURE', 'otherNames': ['Endovascular treatment', 'Mechanical thrombectomy'], 'description': 'Patients will received endovascular thrombectomy', 'armGroupLabels': ['Placebo group', 'rhTNK-tPA group']}]}, 'contactsLocationsModule': {'centralContacts': [{'name': 'Zhongming Qiu, MD', 'role': 'CONTACT', 'email': 'qiuzhongmingdoctor@163.com', 'phone': '13236599269'}, {'name': 'Hongfei Sang, MD', 'role': 'CONTACT', 'email': 'sanghongfei1988@163.com', 'phone': '13738132047'}], 'overallOfficials': [{'name': 'Qingwu Yang, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Neurology, Xinqiao Hospital of the Army Medical University'}, {'name': 'Shunfu Jiang, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Department of Neurology Jingdezhen First People's Hospital"}, {'name': 'Congguo Yin, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hangzhou First Hospital of Westlake University'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ANALYTIC_CODE'], 'timeFrame': 'Related papers published 6 months later, the IPD will be shared', 'ipdSharing': 'YES', 'description': 'study data without patient information', 'accessCriteria': 'yangqwmlys@l63.com'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Xinqiao Hospital of Chongqing', 'class': 'OTHER'}, 'collaborators': [{'name': 'China Shijiazhuang Pharmaceutical Company RECOMGEN PHARMACEUTICAL (GUANGZHOU) CO.,LTD', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Zhongming Qiu', 'investigatorAffiliation': 'Xinqiao Hospital of Chongqing'}}}}