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

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)

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

Study Overview

• Status: Recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Tenecteplase

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Carlos Molina, Dr; Phone Number: 4996 (+34) 93 489 30 00; Email: cmolina@vhebron.net

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Contact: Carlos Molina, Dr.; Phone Number: 4996 (+34) 93 489 30 00; Email: cmolina@vhebron.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tenecteplase (TNK); Drug: Alteplase (tPA) Dose: 0.9 mg/kg Route: Intravenous (IV) infusion	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)
Active Comparator: Alteplase (tPA); Drug: Tenecteplase (TNK) Dose: 0.25 mg/kg Route: Intravenous (IV) bolus injection	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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin scale score at 3 months	Shift analysis of the modified Rankin scale score at 3 months	3 months
Mortality rate	Mortality at 3 months	3 months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of mRS 0-1 at 3 months	Modified Rankin scale score (0-1) rates	3 months
Rates of mRS 0-2 at 3 months	Modified Rankin scale score (0-2) rates	3 months
Rates of pre-interventional recanalization	Recanalization rate	during the procedure
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
First pass TICI 3, final TICI 2b-3	Rates of first pass TICI 3, final TICI 2b-3	immediately after the procedure
Distal embolization during EVT	Rates of distal embolization during EVT	during the procedure
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
Time metrics between TNKCAT and non-TNKCAT centers	Differences in time metrics between TNKCAT and non-TNKCAT centers	at the end of the study
Final infarct volume on follow up CT	Differences in final infarct volume on follow up CT	24-36 hours follow up

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute
• Collaborators: Instituto de Salud Carlos III

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2022
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: November 22, 2022
• First Posted (Actual): November 25, 2022

Study Record Updates

• Last Update Posted (Actual): November 25, 2022
• Last Update Submitted That Met QC Criteria: November 22, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: acute ischemic stroke; large vessel occlusion
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Ischemia; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: 2020-001599-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No