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Extending the Time Window for Tenecteplase by Recanalization of Basilar Artery Occlusion in Posterior Circulation Stroke

NCT ID: NCT05105633

Last Updated: 2023-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

688 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-29

Study Completion Date

2026-12-31

Brief Summary

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Patients presenting to the emergency department with an acute ischemic stroke due to basilar artery occlusion within 24 hours of stroke onset will be assessed to determine their eligibility for randomization into the trial. If the patient gives informed consent they will be randomised 50:50 using a central computerised allocation process to either standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase 0.25mg/kg before undergoing mechanical thrombectomy as required at treating clinician's discretion. The trial is Multi-arm, Multi-stage, prospective, randomised, open-label, blinded endpoint (PROBE) design with seamless phase 2b/3 transition if the intermediate endpoint (recanalization without symptomatic intracerebral hemorrhage) is met in analysis of the first 202 patients. Adaptive sample size re-estimation (Mehta and Pocock) will be performed when 240 patients have completed 3 month follow-up (minimum sample size 320, maximum sample size 688).

Detailed Description

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The study is a Multi-Arm Multi-Stage (MAMS), multiregional, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE), controlled seamless phase 2b/3 trial (2 arm with 1:1 randomisation) with adaptive sample size recalculation in patients with stroke due to basilar artery occlusion. Stage 1 will use the surrogate outcome of recanalization without symptomatic intracerebral hemorrhage (sICH) to establish whether proceeding to Stage 2 is warranted. If results in the first n= 202 patients meet success criteria, the trial will seamlessly convert to a phase 3 design using modified Rankin scale 0-1 at 3 months as the primary outcome (minimum n=320 with interim sample size re-estimation at n=240, maximum sample n=688) using the Mehta and Pocock conditional power method. Each regionally-based stratum will be pooled in the final analysis and analysed as a stratification by geographic region. Randomisation of patients within each stratum will be stratified by the investigator's intention to treat with mechanical thrombectomy (or not) and the investigator's intention to treat with alteplase intravenous thrombolysis should the patient be randomised to the control group (or not). Covariate adjusted minimum sufficient balance randomisation will then be applied to control for age, NIHSS and time from onset-to-randomisation (dichotomized as 0-6 hours vs 6-24 hours). The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0.25mg/kg) ± mechanical thrombectomy administered within 24 hours after symptoms onset, is superior to current best practice (alteplase, rtPA, 0.9mg/kg or standard care/no lysis ± mechanical thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischemic stroke due to basilar artery occlusion. Estimated study duration is 5 years. Patients will participate in the trial for 12 months.

Conditions

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Basilar Artery Occlusion

Keywords

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ischemic stroke basilar artery occlusion Stroke Tenecteplase Tissue Plasminogen Activator Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases Nervous System Diseases Vascular Diseases Cardiovascular Diseases Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Patients will receive either intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds) or standard of care (alteplase 0.9mg/kg or no lysis) +/- mechanical thrombectomy
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intravenous tenecteplase (TNK)

Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).

Group Type EXPERIMENTAL

Tenecteplase

Intervention Type DRUG

Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.

Standard Care (which may include intravenous Alteplase)

Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour).

Group Type ACTIVE_COMPARATOR

Standard Care (which may include intravenous Alteplase)

Intervention Type DRUG

Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour.

Interventions

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Tenecteplase

Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as an intravenous bolus over 5-10 seconds.

Intervention Type DRUG

Standard Care (which may include intravenous Alteplase)

Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as a bolus and the remainder as an infusion over 1 hour.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.
* Patient's age is ≥18 years
* Presence of basilar artery occlusion, proven by CT Angiography or MR Angiography. Basilar artery occlusion is defined as 'potentially retrievable' occlusion at the basilar artery. This can be a partial or complete occlusion.
* Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance and able to manage alone for at least 1 week).
* Local legal requirements for consent have been satisfied.

Exclusion Criteria

* Intracerebral hemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
* Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) \<7 on non-contrast CT, CT Angiography source images or DWI MRI.
* Significant cerebellar mass effect or acute hydrocephalus.
* Established frank hypodensity on non-contrast CT indicating subacute infarction.
* Bilateral extensive brainstem ischemia.
* Strong suspicion of underlying intracranial atherosclerotic disease (e.g diffuse arterial calcifications, basilar stenosis) or dissection which may require immediate neuro-interventional procedure with intracranial stenting and not benefit from intravenous thrombolysis at investigator's discretion.
* Pre-stroke mRS of ≥4 (indicating moderate to severe previous disability).
* Other standard contraindications to intravenous thrombolysis.
* Contraindication to imaging with contrast agents.
* Clinically evident pregnant women.
* Current participation in another research drug treatment protocol.
* Known terminal illness such that the patients would not be expected to survive a year.
* Planned withdrawal of care or comfort care measures.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Melbourne

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bruce Campbell

Role: PRINCIPAL_INVESTIGATOR

University of Melbourne

Fana Alemseged

Role: PRINCIPAL_INVESTIGATOR

University of Melbourne

Locations

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Bankstown-Lidcombe Hospital

Bankstown, New South Wales, Australia

Site Status NOT_YET_RECRUITING

John Hunter Hospital

Newcastle, New South Wales, Australia

Site Status NOT_YET_RECRUITING

Liverpool Hospital

Sydney, New South Wales, Australia

Site Status NOT_YET_RECRUITING

Gold Coast Hospital

Gold Coast, Queensland, Australia

Site Status NOT_YET_RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Alfred Health

Melbourne, Victoria, Australia

Site Status RECRUITING

Austin Hospital

Melbourne, Victoria, Australia

Site Status NOT_YET_RECRUITING

Box Hill Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Monash Health

Melbourne, Victoria, Australia

Site Status NOT_YET_RECRUITING

Royal Melbourne Hospital

Melbourne, Victoria, Australia

Site Status RECRUITING

Western Health

Melbourne, Victoria, Australia

Site Status NOT_YET_RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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Fana Alemseged, MD, PhD

Role: CONTACT

Phone: +6193424424

Email: [email protected]

Amy McDonald, BN

Role: CONTACT

Phone: +6193424424

Email: [email protected]

Facility Contacts

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Megan Miller

Role: primary

Michelle Russell

Role: primary

Megan Miller

Role: primary

Berzenn Urbi

Role: primary

Carol Bendall

Role: primary

Jennifer Cranefield

Role: primary

Andrea Moore

Role: primary

Dennis Young

Role: primary

Tessa Busch

Role: primary

Marie Veronic Hervet

Role: primary

Amy McDonald, BN

Role: primary

Sherisse Celestino

Role: primary

Phoebe Lee

Role: primary

Other Identifiers

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CT21028

Identifier Type: -

Identifier Source: org_study_id