Acute Ischemic Stroke
Conditions
Keywords
acute ischemic stroke, Oral AntiCoagulants, thrombolysis, intravenous tenecteplase administration
Brief summary
The study will randomize patients with acute ischemic stroke and Direct Oral AntiCoagulants (DOAC) ingestion within 48 hours from enrollment (but otherwise eligible for thrombolysis) to administration of intravenous tenecteplase vs. placebo (1:1). Participants will be enrolled at NIH StrokeNet sites across the US and followed for 90-days. The primary aim is to determine the efficacy of intravenous tenecteplase (TNK) vs placebo among acute ischemic stroke patients and to determine the safety of TNK among acute ischemic stroke patients within 4.5 hours of last known well who used DOAC within 48 hours prior to thrombolysis. Efficacy and safety endpoints will be the focus of this proposed Phase III study.
Interventions
DRUGIntravenous tenecteplase (TNK)
Intravenous administration of tenecteplase (TNK) at 0.25 mg/kg for a maximum dose of 25 mg.
DRUGPlacebo
Placebo
Sponsors
Hackensack Meridian Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (18 years or older) with a suspected acute ischemic stroke and clearly disabling deficits * Presenting within 4.5 hours of last known well * Able to initiate intravenous thrombolysis within 4.5 hours of last known well * On recent DOAC therapy (dabigatran, apixaban, rivaroxaban, edoxaban) and known last dose taken within 48 hours from thrombolysis.
Exclusion criteria
* Current or history of intracerebral hemorrhage * Non-disabling deficits * Bleeding disorder (e.g. hemophilia) or advanced liver disease or known INR \> 1.7 within 6 hours * Use of therapeutic low molecular weight heparin or therapeutic dose heparin with elevated PTT * ASPECTS \< 6 or clear hypodensity on CT suggestive of completed infarct * Advanced kidney disease (eGFR \< 30 ml/min) * Known or suspected aortic dissection * Known or high suspicion for infective endocarditis * Surgery within 2 weeks * Intracranial or intraspinal surgery within 3 months * Active internal bleeding or gastrointestinal or urinary tract hemorrhage within 3 weeks * Intracranial neoplasm, arterio-venous malformation, or cavernous malformation * Major head trauma or ischemic stroke within 3 months * Known thrombocytopenia (platelets \< 100,000) * Planned endovascular treatment within 30 minutes of study drug administration (i.e., consent, randomization and administration of study drug must occur at least 30 minutes prior to groin puncture; standard care is not to be delayed and patients in whom endovascular therapy will start sooner will not be enrolled) * Comorbid condition with life expectancy of less than 3 months * Any condition that precludes thrombolytic therapy as determined by site principal investigator * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of intravenous Tenecteplase (TNK) | 90 days post administration | Determine the efficacy of intravenous Tenecteplase (TNK) vs placebo among acute ischemic stroke patients within 4.5 hours of their last known well who used DOAC within 48 hours prior to thrombolysis. The primary endpoint is 90-day modified Rankin Scale (mRS). Modified Rankin Scale is a 6 point tool to assess disability with 0 being no disability and 6 being death. |
| Safety of intravenous TNK | within 36 hours from thrombolysis administration | Determine the safety of intravenous TNK among acute ischemic stroke patients within 4.5 hours of last known well who used DOAC within 48 hours prior to thrombolysis. The primary safety endpoint is symptomatic intracranial hemorrhage (sICH) sICH is defined as any hemorrhage with neurological deterioration in the form of ≥ 4 points increase in the NIHSS, or that leads to death and is identified as the predominant cause of the neurologic deterioration (ECASS III definition) and occurring within 36 hours from thrombolysis administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patients with excellent functional outcome | 90 days post administration | To compare the percentage of patients with excellent functional outcome (mRS 0-1) between intravenous TNK versus placebo. mRS 0-1 at 90-days The endpoint of mRS 0-1 at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment |
| Patients with good functional outcome | 90 days post administration | To compare the percentage of patients with good functional outcome (mRS 0-2) between intravenous TNK versus placebo. mRS 0-2 at 90-days The endpoint of mRS 0-2 at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment |
| Utility weighted mRS between intravenous TNK versus placebo | 90 days post administration | To compare the utility weighted mRS between intravenous TNK versus placebo. Utility weighted mRS The endpoint of Utility mRS at 90 days is a standard outcome used in stroke trials to measure functional improvements after acute treatments such as thrombolysis and endovascular treatment |
Countries
United States
Contacts
CONTACTDanielle Dubenezic
PRINCIPAL_INVESTIGATORShadi Yaghi, MD
Hackensack Meridian Health
Outcome results
None listed