Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III

NCT05141305 | Completed Phase 3 DMC

• 1 other identifier: MK02-2020-02
• Study Type: interventional
• Target: 516
• Locations: 1 country
• Sites: 1

Brief Summary

The trial is a phase 3, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) controlled design. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion within 4.5-24 hours from last known well (including wake-up stroke and unwitnessed stroke) will be randomized 1:1 to 0.25mg/kg intravenous tenecteplase or standard medical treatment.

Conditions

Ischemic Stroke, Acute

Keywords

tenecteplase; alteplase; ischemic stroke; phase 3 trial

Outcome Measures

Primary Outcomes (1)

• Excellent functional outcome

  Proportion of excellent functional outcome defined as an mRS score ≤ 1 at 90 days

  90 days

Secondary Outcomes (9)

• Ordinal distribution of mRS

  90 days

• Favorable functional outcome

  90 days

• Clinical response rate at 72 hours

  72 hours

• The rate of improvement on reperfusion

  24 hours

• NIHSS change from baseline

  7 days

Study Arms (2)

tenecteplase ( 0.25 mg/kg, Max 25 mg )

EXPERIMENTAL

Tenecteplase (0.25 mg/kg) is given as a single, intravenous bolus (within 5-10 seconds) immediately upon randomization. Maximum dose 25mg.

Drug: tenecteplase (0.25 mg/kg, Max 25 mg)

standard medical treatment

ACTIVE COMPARATOR

Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone after randomization at the discretion of local investigators.

Drug: standard medical treatment

Interventions

tenecteplase (0.25 mg/kg, Max 25 mg) DRUG

tenecteplase (0.25 mg/kg) is being used.

tenecteplase ( 0.25 mg/kg, Max 25 mg )

standard medical treatment DRUG

Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone are being used.

Also known as: Aspirin, Clopidogrel

standard medical treatment

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;
• Acute ischemic stroke symptom onset between 4.5 to 24 hours prior to enrolment; including wake-up stroke and unwitnessed stroke, onset time refers to "last-seen normal time";
• Internal carotid artery, middle cerebral artery M1 or M2 occlusion confirmed by CTA/MRA, internal carotid artery, middle cerebral artery M1 or M2 being responsible for signs and symptoms of acute ischemic stroke;
• Pre-stroke modified Rankin scale (mRS) score≤1;
• Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
• Neuroimaging: target mismatch profile on CTP or MRI+MR Perfusion (ischemic core volume \<70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
• Written informed consent from patients or their legally authorized representatives.

You may not qualify if:

• Intended to proceed to endovascular treatment;
• Allergy to tenecteplase;
• Rapidly improving symptoms at the discretion of the investigator;
• NIHSS consciousness score 1a \>2, or epileptic seizure, hemiplegia after seizures ( Todd's palsy ) or other neurological/mental illness such that the patient is not able to cooperate or unwilling to cooperate;
• Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure-lowering treatment;
• Blood glucose \<2.8 or \>22.2 mmol/L (point of care glucose testing is acceptable );
• Active internal bleeding or at high risk of bleeding, e.g., major surgery, trauma or gastrointestinal or urinary tract hemorrhage within the previous 21 days, or arterial puncture at a non-compressible site within the previous 7 days;
• Any known impairment in coagulation due to comorbid disease or anticoagulant use. If on warfarin, then INR \>1.7 or prothrombin time \>15 seconds; use of any direct thrombin inhibitors or direct factor Xa inhibitors during the last 48 hours unless reversal of effect can be achieved with a reversal agent; any full dose heparin/heparinoid during the last 24 hours or with an elevated aPTT greater than the upper limit of normal;
• Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included);
• Ischemic stroke or myocardial infarction in previous 3 months, previous intracranial hemorrhage, severe traumatic brain injury or intracranial or intraspinal operation in previous 3 months, or known intracranial neoplasm, arteriovenous malformation or giant aneurysm;
• Any terminal illness such that the patient would not be expected to survive more than 1 year;
• Unable to perform CTP or PWI;
• Hypodensity in \>1/3 MCA territory on non-contrast CT;
• Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;
• Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100000, China

Location

Related Publications (2)

• Xiong Y, Campbell BCV, Schwamm LH, Meng X, Jin A, Parsons MW, Fisher M, Jiang Y, Che F, Wang L, Zhou L, Dai H, Liu X, Pan Y, Duan C, Xu Y, Xu A, Zong L, Tan Z, Ye W, Wang H, Wang Z, Hao M, Cao Z, Wang L, Wu S, Li H, Li Z, Zhao X, Wang Y; TRACE-III Investigators. Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without Thrombectomy. N Engl J Med. 2024 Jul 18;391(3):203-212. doi: 10.1056/NEJMoa2402980. Epub 2024 Jun 14.

  PMID: 38884324 DERIVED

• Xiong Y, Campbell BCV, Fisher M, Schwamm LH, Parsons M, Li H, Pan Y, Meng X, Zhao X, Wang Y. Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open-label, controlled trial. Stroke Vasc Neurol. 2024 Feb 27;9(1):82-89. doi: 10.1136/svn-2023-002310.

  PMID: 37247876 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Tenecteplase; MAX protein, human; Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; 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; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yongjun Wang, MD, PhD

  Beijing Tiantan Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: December 2, 2021
• Study Start: January 19, 2022
• Primary Completion: January 29, 2024
• Study Completion: February 9, 2024
• Last Updated: April 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)