Clinical trial NCT05626972: Tenecteplase Compared to Alteplase for Patients With Large Vesel Oclusion Suspicion Before Thrombectomy
Official title: A Multi-center, Randomized, Open-label Blinded Endpoint (PROBE), Phase III Study, for the Comparation of Tenecteplase (TNK) Versus Alteplase, With a 1:1 Allocation, Before Thrombectomy in Patients With Acute Ischemic Stroke and Large Vessel Occlusion Suspicion in Catalonia (TNK-CAT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: acute ischemic stroke
large vessel occlusion
Lead sponsor: Hospital Universitari Vall d'Hebron Research Institute
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2022-11-25
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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 exclusion criteria:

* Clinical symptoms suggestive of bilateral stroke or stroke in multiple territories.
* Cerebral vasculitis.
* CT or MRI evidence of hemorrhage
* Significant mass effect with midline shift.
* Evidence of intracranial tumor.
* Subjects with known occlusions in multiple vascular territories (e.g., bilateral anterior circulation, or anterior/posterior circulation).

Primary outcomes:
measure: Modified Rankin scale score at 3 months
timeFrame: 3 months
measure: Mortality rate
timeFrame: 3 months
measure: Symptomatic intracerebral haemorrhage (ICH) and neurological deterioration
timeFrame: 24 -36hours
Secondary outcomes:
measure: Rates of mRS 0-1 at 3 months
timeFrame: 3 months
measure: Rates of mRS 0-2 at 3 months
timeFrame: 3 months
measure: Rates of pre-interventional recanalization
timeFrame: during the procedure
measure: Dramatic clinical recovery before endovascular treatment (EVT)
timeFrame: before the procedure
measure: First pass TICI 3, final TICI 2b-3
timeFrame: immediately after the procedure
measure: Distal embolization during EVT
timeFrame: during the procedure
measure: Needle-to-groin times and DIDO times
timeFrame: immediately after the procedure
measure: Time metrics between TNKCAT and non-TNKCAT centers
timeFrame: at the end of the study
measure: Final infarct volume on follow up CT
timeFrame: 24-36 hours follow up
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
Study officials:
References: