Randomization to Extend Stroke Intravenous ThromboLysis In Evolving Non-Large Vessel Occlusion With TNK (RESILIENT (EXTEND-IV)

  • STATUS
    Recruiting
  • End date
    May 29, 2024
  • participants needed
    642
  • sponsor
    Hospital Moinhos de Vento
Updated on 29 April 2022

Summary

A phase III, randomized, multi-center clinical trial that will examine whether treatment with intravenous TNK is superior to placebo in patients who suffer a non-large vessel occlusion ischemic stroke within 4.5-12 hours from time last seen well. The randomization employs a 1:1 ratio of intravenous thrombolysis with Tenecteplase (TNK) versus placebo in patients who suffer a non-large vessel occlusion ischemic stroke between 4.5 and 12 hours from time last seen well (TLSW) and have evidence of salvageable brain tissue on perfusion imaging.

Description

Prospective, multi-center, randomized, controlled, double blinded trial with an adaptive design and population enrichment. The randomization employs a 1:1 ratio of intravenous thrombolysis with Tenecteplase (TNK) versus placebo in patients who suffer a non-large vessel occlusion ischemic stroke between 4.5 and 12 hours from time last seen well (TLSW) and have evidence of salvageable brain tissue on perfusion imaging. Randomization will be done under a minimization process using age (≤70 vs. >70 years), baseline NIHSS (≤10 vs. >10), baseline infarct volume (≤15mL vs. >15-30mL vs. >30-50mL), perfusion mismatch volume (≤15mL vs. >15-30mL vs. >30-50mL), therapeutic window (4.5-9 or 9-12 hours after TLKW), and clinical site. The candidate enriched populations that the trial considers are based on time last known well (TLKW) to randomization (4.5-9 vs. 9-12 hours) and mismatch volumes as measured using Mismatch on MRP-DWI or CTP-rCBF maps (>40 cc vs. >30cc vs. >20cc vs. >10cc). For the primary endpoint, subjects will be followed for 90 days post-randomization.

Details
Condition Ischemic Stroke, Acute
Treatment Placebo, Intravenous Tenecteplase
Clinical Study IdentifierNCT05199662
SponsorHospital Moinhos de Vento
Last Modified on29 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

\. Acute ischemic stroke where patient is ineligible for IV thrombolytic treatment with Alteplase due to onset >4.5 hours and is ineligible for endovascular treatment under standard of care due to absence of proximal arterial occlusion (e.g. intracranial ICA, MCA-M1 and dominant M2 segments, and vertebrobasilar arteries)
Dominant M2 segment is defined is a division supplying >50% of the MCA territory vs co-dominant supplying 50% of the MCA territory vs non-dominant supplying <50% of the MCA territory. 2. No significant pre-stroke functional disability (mRS ≤2). 3. Evidence of a disabling deficit including significant aphasia, neglect, hemianopsia, or hemiparesis and/or baseline NIHSS score ≥4 points (obtained prior to randomization). 4. Age ≥18 years (no upper age limit). 5. The presence of a Target Mismatch defined as
Ischemic Core < 50cc) (defined on NCCT/CTP or DWI-MRI)
e-volume NCCT can be used to exclude patients if the investigator believes that
its volume assessment is more reliable than the CTP volume in any particular
case
b. Mismatch Volume (TMax >6sec lesion - Core volume lesion) >10cc c. Mismatch
Ratio >1.4 6. Patient treatable within 4.5-12 hours of symptom onset. Symptoms
onset is defined as point in time the patient was last seen well (at
baseline). Treatment start is defined as initiation of IV TNK or placebo
infusion. 7. Informed consent obtained from patient or acceptable patient
surrogate

Exclusion Criteria

Intracranial hemorrhage (ICH) identified by CT or MRI
Rapidly improving symptoms, particularly if in the judgment of the managing clinician that the improvement is likely to result in the patient having an NIHSS score of < 4 at randomization
Pre-stroke mRS score of ≥ 2 (indicating previous disability)
Contra indication to imaging with MR or CT with contrast agents
Infarct core >1/3 MCA territory qualitatively or >50 mL quantitatively (determined by DWI lesion on MR)
Participation in any investigational study in the previous 30 days
Any terminal illness such that patient would not be expected to survive more than 1 year)
Baseline platelet count < 100.000/µL
Woman of childbearing potential who is known to be pregnant or who has a positive pregnancy test on admission
Previous stroke within last three months
Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH), arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than meningioma
Current use of oral anticoagulants and a prolonged prothrombin time (INR > 1.6)
Use of heparin, except for low dose subcutaneous heparin, in the previous 48 hours and a prolonged partial thromboplastin time exceeding the upper limit of the local laboratory normal range
Use of glycoprotein IIb - IIIa inhibitors within the past 72 hours. Use of single agent oral platelet inhibitors (clopidogrel or low-dose aspirin) prior to study entry is permitted
Clinically significant hypoglycemia
Uncontrolled hypertension defined by a blood pressure > 185 mmHg systolic or >110 mmHg diastolic on at least 2 separate occasions at least 10 minutes apart, or requiring aggressive treatment to reduce the blood pressure to within these limits. The definition of "aggressive treatment" is left to the discretion of the responsible Investigator
Hereditary or acquired hemorrhagic diathesis
Gastrointestinal or urinary bleeding within the preceding 21 days
Major surgery within the preceding 14 days which poses risk in the opinion of the Investigator
Exposure to a thrombolytic agent within the previous 72 hours
Subject participating in a study involving an investigational drug or device that would impact this study
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