Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5 (TRACE-5)

Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5 Improving Neurological Functional Outcomes in Basilar Artery Occlusion With Tenecteplase in Extended Time Window: Multicentre, Prospective, Open-label, Blinded Endpoint (PROBE), Phase 3, Randomized Controlled Trial

The trial is a multicentre, prospective, open-label, blinded endpoint (PROBE), phase 3, randomized controlled design. Patients with acute ischemic stroke due to basilar artery occlusion presenting within 24 hours will be randomized 1:1 to intravenous tenecteplase (0.25mg/kg, maximum 25mg) ± thrombectomy or 'best practice'which may be alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke, Acute
• Intervention / Treatment: Drug: Tenecteplase; Drug: Best Practice (which may include intravenous Alteplase)

Detailed Description

The study will be a multicentre, prospective, open-label, blinded endpoint (PROBE), randomized controlled trial (2 arm with 1:1 randomization) in patients with acute ischemic stroke due to basilar artery occlusion presenting to hospital within 24 hours of symptom onset.

Patients will be required to have complete or partial occlusion of the basilar artery on baseline computed tomography angiography (CTA)/magnetic resonance angiography (MRA), defined as 'potentially retrievable' thrombus in the basilar artery. Thrombectomy is permitted within 24 hours as part of standard care but is not mandatory.

Patients will be randomized to treatment with either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg within 4.5 hours from stroke onset) or intravenous tenecteplase (0.25mg/kg, maximum 25mg). Time of onset of symptoms is defined as described by the patient or witness; if unknown, it is considered to be the last time the patient was seen well. In patients presenting with mild (e.g. vertigo, dizziness, headache, diplopia, dysarthria) stuttering symptoms followed by sudden onset of clinical deterioration with decrease in conscious state or moderate to severe motor deficits, the time of deterioration in clinical state is taken as the estimated time of basilar artery occlusion.

• Study Type: Interventional
• Enrollment (Estimated): 452
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yunyun Xiong, MD, PhD; Phone Number: 86-15710088948; Email: xiongyunyun@bjtth.org

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100070
      • Recruiting
      • Beijing Tian Tan Hospital, Capital Medical University
      • Contact: Yunyun Xiong, MD, PhD; Phone Number: 86-15710088948; Email: xiongyunyun@bjtth.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18.
2. Patients presenting with posterior circulation ischemic stroke symptoms due to partial or complete basilar artery occlusion within 24 hours from symptom onset (or clinical deterioration/coma) or the time the patient was last known to be well.
3. Presence of a basilar artery occlusion, proven by CT Angiography. Basilar artery occlusion will be defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
4. Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
5. Local legal requirements for consent have been satisfied.

Exclusion Criteria:

1. Intracerebral haemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
2. Posterior circulation Acute Stroke Prognosis Early CT Score (PC-ASPECTS) on CT/ CTA-Source Images<6.
3. Significant cerebellar mass effect or acute hydrocephalus.
4. Established frank hypodensity on non-contrast CT indicating subacute infarction.
5. Bilateral extensive brainstem ischemia.
6. Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability).
7. Other standard contraindications to intravenous thrombolysis.
8. Contraindication to imaging with contrast agents.
9. Clinically evident pregnant women.
10. Vessel imaging showing both anterior and posterior circulation large vessel occlusion.
11. Current participation in another research drug treatment protocol.
12. Known terminal illness such that the patients would not be expected to survive a year.
13. Planned withdrawal of care or comfort care measures.
14. 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.

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; Intravenous tenecteplase (0.25mg/kg, maximum 25mg) within 24 hours ± thrombectomy at treating clinician's discretion	Drug: Tenecteplase; Intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus within 5-10 seconds) within 24 hours ± thrombectomy at treating clinician's discretion; Other Names: TNK-tPA; rhTNK-tPA
Active Comparator: Best Practice (which may include intravenous Alteplase); Intravenous alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion	Drug: Best Practice (which may include intravenous Alteplase); Intravenous alteplase (0.9mg/kg) within 4.5 hours from stroke onset or standard care (no lysis) ± thrombectomy at treating clinician's discretion; Other Names: rt-PA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) 0-1 or return to baseline mRS	The proportion of patients with Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2-3) at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS) 0-2 or return to baseline mRS	Proportion of patients with Modified Rankin Scale (mRS) 0-2 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).	3 months
Modified Rankin Scale (mRS) 0-3 or return to baseline mRS	Proportion of patients with Modified Rankin Scale (mRS) 0-3 or return to baseline mRS at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).	3 months
Ordinal analysis of the Modified Rankin Scale (mRS)	Ordinal analysis of the Modified Rankin Scale (mRS), merging category 5-6, at 3 months. Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).	3 months
Early neurological improvement	Proportion of patients achieving early clinical improvement (reduction in acute - 72 hour National Institutes of Health Stroke Scale [NIHSS] score of ≥8 or 72 hour NIHSS 0-1).	72 hours
Successful reperfusion	Proportion of patients with complete occlusion at baseline who achieve expanded Thrombolysis In Cerebral Infarction score (eTICI) 2b/3 on initial digital subtraction angiography (DSA) run prior to thrombectomy.	initial DSA run prior to thrombectomy
Symptomatic intracranial hemorrhage (sICH)	Proportion of patients with Symptomatic intracranial hemorrhage (sICH) defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 hours of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.	36 hours
All-cause mortality	All-cause mortality within 90 days.	90 days
Severe disability or death	Proportion of patients with Modified Rankin Scale (mRS) 5-6 at 90 days (severe disability or death). Scores on the modified Rankin scale range from 0 (no neurologic deficit) to 6 (death).	90 days
Clinical deterioration	Proportion of patients with partially occlusive thrombus at baseline who have clinical deterioration within 24 hours leading to further treatment (e.g. endovascular thrombectomy).	24 hours
Vessel recanalization	Vessel recanalization rate evaluated by CT or MR angiography within 24+/-6 hours (if performed).	24+/-6 hours

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun Wang, MD, Beijing Tiantan Hospital; Principal Investigator: Bruce Campbell, MD, PhD, University of Melbourne; Study Director: Fana Alemseged, MD, PhD, University of Melbourne; Study Director: Yunyun Xiong, MD, PhD, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: January 7, 2024
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Estimated): January 15, 2024
• Last Update Submitted That Met QC Criteria: January 11, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ischemic stroke; rt-PA; phase III trial; rhTNK-tPA; basilar artery occlusion
• 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; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Tenecteplase
• Other Study ID Numbers: CSA2023YJ002

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
• product manufactured in and exported from the U.S.: No