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

Last updated: December 5, 2023
Sponsor: University of Melbourne
Overall Status: Active - Recruiting

Phase

2/3

Condition

N/A

Treatment

Tenecteplase

Standard Care (which may include intravenous Alteplase)

Clinical Study ID

NCT05105633
CT21028
  • Ages > 18
  • All Genders

Study Summary

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).

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients presenting with posterior circulation ischemic stroke symptoms due to partialor complete basilar artery occlusion within 24 hours from symptom onset (or clinicaldeterioration/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 thebasilar artery. This can be a partial or complete occlusion.
  • Premorbid mRS ≤3 (independent function or requiring only minor domestic assistance andable to manage alone for at least 1 week).
  • Local legal requirements for consent have been satisfied.

Exclusion

Exclusion Criteria:

  • Intracerebral hemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baselineimaging.
  • Posterior circulation Acute Stroke Prognosis Early CT score (pc-ASPECTS) <7 onnon-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 diffusearterial calcifications, basilar stenosis) or dissection which may require immediateneuro-interventional procedure with intracranial stenting and not benefit fromintravenous 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 thepatient if study therapy is initiated or affect the participation of the patient inthe study.

Study Design

Total Participants: 688
Treatment Group(s): 2
Primary Treatment: Tenecteplase
Phase: 2/3
Study Start date:
November 29, 2021
Estimated Completion Date:
December 31, 2026

Study Description

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.

Connect with a study center

  • Bankstown-Lidcombe Hospital

    Bankstown, New South Wales
    Australia

    Site Not Available

  • John Hunter Hospital

    Newcastle, New South Wales
    Australia

    Site Not Available

  • Liverpool Hospital

    Sydney, New South Wales
    Australia

    Site Not Available

  • Gold Coast Hospital

    Gold Coast, Queensland
    Australia

    Site Not Available

  • Princess Alexandra Hospital

    Woolloongabba, Queensland 4102
    Australia

    Active - Recruiting

  • Royal Adelaide Hospital

    Adelaide, South Australia
    Australia

    Active - Recruiting

  • Alfred Health

    Melbourne, Victoria
    Australia

    Active - Recruiting

  • Austin Hospital

    Melbourne, Victoria
    Australia

    Site Not Available

  • Box Hill Hospital

    Melbourne, Victoria
    Australia

    Active - Recruiting

  • Monash Health

    Melbourne, Victoria
    Australia

    Site Not Available

  • Royal Melbourne Hospital

    Melbourne, Victoria
    Australia

    Active - Recruiting

  • Western Health

    Melbourne, Victoria
    Australia

    Site Not Available

  • Fiona Stanley Hospital

    Murdoch, Western Australia 6150
    Australia

    Active - Recruiting

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