Tenecteplase Compared to Alteplase for Patients With Large Vesel Oclusion Suspicion Before Thrombectomy

Acute Ischemic Stroke Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05626972
• Other study ID #: 2020-001599-13
• Status: Recruiting
• Phase: Phase 3
• Start date: May 27, 2022
• Est. completion date: May 2024

Study information

• Verified date: November 2022
• Source: Hospital Universitari Vall d'Hebron Research Institute
• Contact: Carlos Molina, Dr
• Phone: (+34) 93 489 30 00
• Email: cmolina[@]vhebron.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: May 2024
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Tenecteplase
Patients will be randomized 1:1 to standard dose tPA (0.9 mg/kg) or TNK (0.25mg/kg) before endovascular therapy (EVT)

Locations

Country	Name	City	State
Spain	Hospital Universitari Vall d'Hebron	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Hospital Universitari Vall d'Hebron Research Institute	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Modified Rankin scale score at 3 months	Shift analysis of the modified Rankin scale score at 3 months	3 months
Primary	Mortality rate	Mortality at 3 months	3 months
Primary	Symptomatic intracerebral haemorrhage (ICH) and neurological deterioration	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.	24 -36hours
Secondary	Rates of mRS 0-1 at 3 months	Modified Rankin scale score (0-1) rates	3 months
Secondary	Rates of mRS 0-2 at 3 months	Modified Rankin scale score (0-2) rates	3 months
Secondary	Rates of pre-interventional recanalization	Recanalization rate	during the procedure
Secondary	Dramatic clinical recovery before endovascular treatment (EVT)	Dramatic clinical recovery before EVT (Improvement in > 8 points in the NIHSS score or NIHSS score < 2 before groin puncture)	before the procedure
Secondary	First pass TICI 3, final TICI 2b-3	Rates of first pass TICI 3, final TICI 2b-3	immediately after the procedure
Secondary	Distal embolization during EVT	Rates of distal embolization during EVT	during the procedure
Secondary	Needle-to-groin times and DIDO times	Differences in needle-to-groin times in Mothership patients and in DIDO times in Drip-and-Ship patients.	immediately after the procedure
Secondary	Time metrics between TNKCAT and non-TNKCAT centers	Differences in time metrics between TNKCAT and non-TNKCAT centers	at the end of the study
Secondary	Final infarct volume on follow up CT	Differences in final infarct volume on follow up CT	24-36 hours follow up