Safety and Efficacy of Intra-arterial Tenecteplase for Noncomplete Reperfusion of Intracranial Occlusions

Study Overview
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Brief Summary
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TECNO is a multicenter, prospective, randomized, open label, blinded endpoint (PROBE) proof-of-concept trial evaluating if additional administration of intra-arterial Tenecteplase (TNK) improves reperfusion in patients with incomplete mechanical thrombectomy (MT). For this purpose, 156 adult participants experiencing an acute ischemic stroke due to a large vessel occlusion with incomplete reperfusion with residual occlusions after MT will be randomly assigned to receive 3mg intra-arterial (IA) TNK or best medical treatment. Recruitment will occur at 20 academic tertiary stroke care centers in Switzerland, Spain, Belgium, and Germany and patients are followed up for 90 days after the index event. Showing superiority for reperfusion outcomes would have a major impact on the future management of stroke patients.

Official Title
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Safety and Efficacy of Intra-arterial Tenecteplase for Noncomplete Reperfusion of Intracranial Occlusions

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: Tenecteplase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Informed consent Age ≥18 years Clinical signs consistent with an acute ischemic stroke Patient had an initial large vessel occlusion in the anterior circulation defined as intracranial ICA, M1 or M2. Patient has undergone endovascular stroke treatment Onset to randomization no later than < 345 minutes after symptom-onset/last-seen well. Incomplete reperfusion defined as For ICA/M1: TICI2b/2c (50-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist). For M2: TICI2a/2b/2c (1-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist). ICA/M1/M2 with TICI3 reperfusion (MCA territory) but emboli to the ACA territory without mechanically amendable target-occlusion (as per definition by the interventionalist). Signs of early ischemic changes of non-contrast CT Alberta Stroke Program Early CT Score (ASPECTS) ≥5 (for DWI-ASPECTS ≥ 4, for DWI-ASECTS: a region must have diffusion abnormality in 20% or more of its volume to be considered DWI-ASPECTS positive) Exclusion Criteria Acute intracranial hemorrhage Contraindication to MRI (e.g. pacemaker) Patients with both, anterior and middle cerebral artery embolizations during the procedure Tandem occlusion requiring cervical stenting Any severe bleeding within the past 6 months Major surgery in the past 2 months Intake of direct oral anticoagulants <12h or Vitamin K Antagonist with INR >1.3 Platelets < 50,000 Non-controlled hypertension (defined as SBP >185 mmHg or DBP >110 mmHg refractory to treatment)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Best Medical Treatment (standard of care)<br>Patients will receive standard of care as per current ESO guidelines. | |
| Experimental: Intra-arterial Tenecteplase<br>Patients will receive intra-arterial administration of Tenecteplase using a standard approved microcatheter. | Drug: Tenecteplase<br>* Patients randomized to IA treatment will receive IA TNK via a standard approved microcatheter positioned as close as possible to the residual occlusion site or as distal as possible in the originating vessel if multiple residual occlusions exists.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early reperfusion of the residual intracranial occlusion(s) | Defined by reperfusion improvement on angiography images | 25 minutes after randomization | 
| Late reperfusion of the residual intracranial occlusion(s) | Defined by complete reperfusion on perfusion imaging | 24 hours ±6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of disability or dependence assessed by the modified ranking scale (mRS) (shift analysis) | mRS | 90 days+/-15 days | 
| Normalized change in National Institute of Health Score Scale (NIHSS) | NIHSS | 24 hours +/- 6 hours post-randomization | 
| Change in National Institute of Health Score Scale (NIHSS) | NIHSS | 90 days +/- 15 days post-randomization | 
| Quality of life as assessed by the EuroQol 5D-3L (EQ-5D-3L) | EuroQol 5D-3L | 90 days +/- 15 days | 
| All-cause mortality | Mortality | 90 days |