Extending the time window for Tenecteplase by Effective RecanalizatioN of bAsilar artery occLusion in patients with POSTerior circulation stroke (POST ETERNAL)
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Not specified
- Sponsor
- Centre Hospitalier Regional Universitaire De Tours
- Enrollment
- 120
- Locations
- 15
- Primary Endpoint
- 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.
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
The primary objective of the study is to test the hypothesis that the thrombolytic tenecteplase (TNK, 0.25mg/kg) administered within 24 hours after symptom onset ± thrombectomy, is superior to current best practice (alteplase, rtPA, 0.9mg/kg within 4.5 hours of stroke onset or standard care/no lysis ± thrombectomy) in achieving excellent functional outcome (mRS 0-1) or return to the premorbid modified Rankin Scale at 90 days in patients with acute ischaemic stroke due to basilar artery occlusion.
Detailed 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.
Investigators
Coordinating Investigator
Scientific
Centre Hospitalier Regional Universitaire De Tours
Eligibility Criteria
Inclusion Criteria
- •Patient presenting with posterior circulation ischaemic 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.
- •Presence of a basilar artery occlusion on CT Angiography or MR Angiography. Basilar artery occlusion will be 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).
- •Affiliated to a French social security scheme or equivalent.
- •Written informed consent obtained from the participant, from her/his next of kin or trusted person. Use of the emergency inclusion procedure if a next of kin or trusted person cannot be contacted. When a subject is no longer incapacitated, informed consent to continue participation will be obtained from the subject.
Exclusion Criteria
- •Intracerebral haemorrhage (ICH) or other diagnosis (e.g. tumour) identified by baseline imaging.
- •Contraindication to imaging with contrast agents.
- •Patient deprived of their liberty by judicial/administrative decision or subject to any legal protection measures (guardianship or trusteeship).
- •Clinically evident pregnant woman.
- •Current participation in another research drug treatment protocol.
- •Known terminal illness such that the patients would not be expected to survive a year.
- •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.
- •Warfarin - thrombolysis can be used if point-of-care INR≤1.4 or laboratory INR≤1.
- •Dabigatran – If dabigatran is known or suspected to have been taken within last 48 hours then Idarucizumab 5g IV bolus should be given prior to thrombolysis.
- •Apixaban/Rivaroxaban - If Apixaban/Rivaroxaban is known to have been taken in last 12 hours then patient cannot be enrolled. If unclear, order urgent aPTT, INR, anti-Xa level: patient can be enrolled if appropriately calibrated anti-Xa level indicates <10 ng/mL apixaban or <100 ng/mL rivaroxaban.
Outcomes
Primary Outcomes
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.
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.
Secondary Outcomes
- Proportion of patients with mRS 0-2 or return to baseline mRS at 3 months.
- Proportion of patients with mRS 0-3 or return to baseline mRS at 3 months.
- Ordinal analysis of the mRS, merging category 5-6, at 3 months.
- Proportion of patients achieving early clinical improvement (reduction in acute –72 hour NIHSS score of ≥8 or 72 hour NIHSS 0-1).
- Proportion of patients with complete occlusion at baseline who achieve eTICI 2b/3 [14] on initial digital subtraction angiography run prior to thrombectomy.
- Proportion of patients with sICH defined as parenchymal haemorrhage type 2 (PH2), subarachnoid haemorrhage, and/or intraventricular haemorrhage within 36 of treatment, combined with a neurological deterioration of ≥4 points on the NIHSS from baseline, or leading to death.
- Proportion of patients with mRS 5-6 at 90 days (severe disability or death).
- All-cause mortality within 90 days.
- Quality of Life assessment (EQ-5D) at 3 and 12 months.