Acute Ischemic Stroke
Conditions
Keywords
acute ischemic stroke, large vessel occlusion
Brief summary
Background: The TNKCAT trial represents an innovative approach to optimize timely reperfusion in the Mothership and Drip-and-Ship scenarios. The logistic advantage of a single bolus infusion of TNK (compared to 1-h infusion of tPA) would markedly reduce the needle-to-groin and Door-in- door-out time. The implementation of a quality improvement package (QIP) in the TNKCAT trial would directly improve the quality and efficiency of the Health Care System. In addition, an improvement of transfer models would reduce the cost of unnecessary transfers, together with the fact that TNK is up to 50% less expensive than tPA, makes the TNKCAT in firm line with the sustainability strategy of the National Health Care system. Outcomes: The aim of the present study is to determine the safety and efficacy of TNK (0.25mh/kg) compared to tPA (0.9 mg/kg) in patients with Large Vessel Occlusion (LVO) suspicion, candidates for thrombectomy, in both Mothership and Drip-and-Ship scenarios. Study Duration: 2 years. Patients will participate in the trial for 3 months. Study design: Multicentre, prospective, randomized open-label blinded endpoint (PROBE) phase III study in acute stroke patients with LVO suspicion within 4.5 hours of stroke onset, candidates for EVT. Patients will be randomized 1:1 to standard dose tPA (0.9 mg/kg) or TNK (0.25mg/kg) before EVT. Clinical, imaging and outcome data will be collected at baseline, 24-36 hours, day 3, day 5 and day 90. Estimated enrollment: 500 patients
Interventions
DRUGTenecteplase
Patients will be randomized 1:1 to standard dose tPA (0.9 mg/kg) or TNK (0.25mg/kg) before endovascular therapy (EVT)
Sponsors
Instituto de Salud Carlos III
Hospital Universitari Vall d'Hebron Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Clinical outcome at day 90 will be obtained by centralized telephone call of the mRS in a blinded manner by certified personnel of the Catalan Stroke Program.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients eligible to undergo intravenous thrombolysis (tPA or TNK) within 4.5 hours after the onset of ischemic stroke. * Suspicion of Cerebral vascular occlusion on brain imaging. * Age \>18 years old * Men and women (women with child-bearing potential are excluded, unless pregnancy test negative/ confirmed menstrual period/ postmenopausal or hysterectomy). * A new focal disabling neurologic deficit consistent with acute cerebral ischemia. * Informed consent obtained from subject or acceptable subject surrogate (i.e. next of kin, or legal representative), or Differed Inform Consent (DIC) to avoid any delay in the initiation of iv thrombolysis. The DIC will be sign by the patient or next of kin at any time after the tPA or TNK treatment is started.
Exclusion criteria
* Patients with severe preexisting disability, defined as a modified Rankin scale score \>3. * Glasgow Coma Scale score ≤ 7. * Known hemorrhagic diathesis, coagulation factor deficiency, or antivitamin K oral anticoagulant therapy with INR \>3.0. Subjects on factor Xa inhibitors (e.g. apixaban) or direct thrombin inhibitors are eligible for participation. * Severe, sustained and uncontrollable hypertension (systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg). * Serious, advanced, or terminal illness with anticipated life expectancy of less than 3 months. * Patients that are unlikely to be available for a 90-day follow-up (e.g. no fixed home address, visitor from overseas). * Patient participating in a randomized study, involving an investigational drug or device that would impact this study. * Suspicion of aortic dissection presumed septic embolus, or suspicion of bacterial endocarditis. Imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Rankin scale score at 3 months | 3 months | Shift analysis of the modified Rankin scale score at 3 months |
| Mortality rate | 3 months | Mortality at 3 months |
| Symptomatic intracerebral haemorrhage (ICH) and neurological deterioration | 24 -36hours | Symptomatic ICH defined as intracerebral haemorrhage (PH2) within 36 hours of treatment, combined with neurological deterioration leading to an increase of ≥ 4 points on the National institute of Health Stroke Scale (NIHSS) from baseline, or the lowest NIHSS value between baseline and 24 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dramatic clinical recovery before endovascular treatment (EVT) | before the procedure | Dramatic clinical recovery before EVT (Improvement in \> 8 points in the NIHSS score or NIHSS score \< 2 before groin puncture) |
| First pass TICI 3, final TICI 2b-3 | immediately after the procedure | Rates of first pass TICI 3, final TICI 2b-3 |
| Distal embolization during EVT | during the procedure | Rates of distal embolization during EVT |
| Rates of mRS 0-1 at 3 months | 3 months | Modified Rankin scale score (0-1) rates |
| Time metrics between TNKCAT and non-TNKCAT centers | at the end of the study | Differences in time metrics between TNKCAT and non-TNKCAT centers |
| Final infarct volume on follow up CT | 24-36 hours follow up | Differences in final infarct volume on follow up CT |
| Needle-to-groin times and DIDO times | immediately after the procedure | Differences in needle-to-groin times in Mothership patients and in DIDO times in Drip-and-Ship patients. |
| Rates of mRS 0-2 at 3 months | 3 months | Modified Rankin scale score (0-2) rates |
| Rates of pre-interventional recanalization | during the procedure | Recanalization rate |
Countries
Spain
Contacts
Primary ContactCarlos Molina, Dr
Outcome results
None listed