Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE III)

A Phase 3, Multicenter, Prospective, Randomized, Open-label, Blinded-endpoint (PROBE) Controlled Trial of Tenecteplase Versus Standard Medical Treatment for Acute Ischemic Stroke Due to Anterior Circulation Large Vessel Occlusion With Perfusion Mismatch up to 24 Hours of Symptom Onset

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.

Study Overview

• Status: Completed
• Conditions: Ischemic Stroke, Acute
• Intervention / Treatment: Drug: standard medical treatment; Drug: tenecteplase (0.25 mg/kg, Max 25 mg)

Detailed Description

The study will be a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), controlled phase 3 trial (2 arms with 1:1 randomization) in ischemic stroke due to anterior circulation large vessel occlusion with perfusion mismatch up to 24 hours of symptom onset. The target mismatch profiles on CTP or MRI perfusion weighted imaging include ischemic core volume <70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL demonstrated by a certified automatic software. The minimum sample size is 516 patients.

• Study Type: Interventional
• Enrollment (Actual): 516
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Tiantan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old;
2. 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";
3. 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;
4. Pre-stroke modified Rankin scale (mRS) score≤1;
5. Baseline National Institutes of Health Stroke Scale (NIHSS) 6-25 (inclusive);
6. Neuroimaging: target mismatch profile on CTP or MRI+MR Perfusion (ischemic core volume <70 mL, mismatch ratio≥1.8 and mismatch volume≥15 mL;
7. Written informed consent from patients or their legally authorized representatives.

Exclusion Criteria:

1. Intended to proceed to endovascular treatment;
2. Allergy to tenecteplase;
3. Rapidly improving symptoms at the discretion of the investigator;
4. 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;
5. Persistent blood pressure elevation (systolic ≥180 mmHg or diastolic ≥100 mmHg), despite blood pressure-lowering treatment;
6. Blood glucose <2.8 or >22.2 mmol/L (point of care glucose testing is acceptable );
7. 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;
8. 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;
9. Known defect of platelet function or platelet count below 100,000/mm3 (NB patients taking antiplatelet medication can be included);
10. 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;
11. Any terminal illness such that the patient would not be expected to survive more than 1 year;
12. Unable to perform CTP or PWI;
13. Hypodensity in >1/3 MCA territory on non-contrast CT;
14. Acute or past intracerebral hemorrhage (ICH) identified by CT or MRI;
15. Multiple arterial occlusion (bilateral MCA occlusion, MCA occlusion accompanied with basilar occlusion);
16. Pregnant women, nursing mothers, or reluctant to use effective contraceptive measures during the period of trial;
17. Unlikely to adhere to the trial protocol or follow-up;
18. 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;
19. Participation in other interventional clinical trials within the previous 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tenecteplase ( 0.25 mg/kg, Max 25 mg ); 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); tenecteplase (0.25 mg/kg) is being used.
Active Comparator: standard medical treatment; Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone after randomization at the discretion of local investigators.	Drug: standard medical treatment; Aspirin combined with clopidogrel, aspirin alone, or clopidogrel alone are being used.; Other Names: Aspirin, Clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Excellent functional outcome	Proportion of excellent functional outcome defined as an mRS score ≤ 1 at 90 days	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIHSS change from baseline	NIHSS change from baseline at 7 days	7 days
Adverse events ( AEs ) / serious adverse events ( SAEs )	Rate of adverse events ( AEs ) / serious adverse events ( SAEs ) within 90 days	90 days
Ordinal distribution of mRS	Ordinal distribution of mRS at 90 days.	90 days
Favorable functional outcome	Proportion of favorable functional outcome defined by an mRS score ≤ 2 point at 90 days	90 days
Clinical response rate at 72 hours	Clinical response rate at 72 hours defined by an improvement on NIHSS score ≥8 points compared with the initial deficit or a score ≤1.	72 hours
The rate of improvement on reperfusion	The rate of improvement on reperfusion at 24 hours (improved by 90% on Tmax>6s)	24 hours
Symptomatic intracranial hemorrhage	Proportion of symptomatic intracranial hemorrhage (sICH) within 36 hours (as defined by The European Cooperative Acute Stroke Study III criteria [ECASSIII])	36 hours
Mortality	Rate of death from any cause within 90 days	90 days
Systemic bleeding	Rate of systemic bleeding at 90 days (as defined by The Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO]: moderate and severe bleeding)	90 days

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Study Director: Yongjun Wang, MD, PhD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2022
• Primary Completion (Actual): January 29, 2024
• Study Completion (Actual): February 9, 2024

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: November 19, 2021
• First Posted (Actual): December 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 28, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: ischemic stroke; tenecteplase; alteplase; phase 3 trial
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Tenecteplase
• Other Study ID Numbers: MK02-2020-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No