Clinical trial NCT05499832: Safety and Efficacy of Intra-arterial Tenecteplase for Noncomplete Reperfusion of Intracranial Occlusions
Official title: Safety and Efficacy of Intra-arterial Tenecteplase for Noncomplete Reperfusion of Intracranial Occlusions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Ischemic Stroke
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2022-08-12
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria

* Informed consent
* Age ≥18 years
* Clinical signs consistent with an acute ischemic stroke
* Patient had an initial vessel occlusion in the anterior or posterior circulation defined as intracranial ICA, M1, M2, M3, A1, A2, P1 or P2
* Patient has undergone endovascular stroke treatment
* Onset to randomization no later than \&lt; 705 minutes (11h 45min) after symptom-onset/last-seen well.
* Incomplete reperfusion defined as any of the following:

  1. For ICA/M1: TICI2b/2c (50-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist).
  2. For A1/A2, P1/P2, M2/M3: TICI2a/2b/2c (1-99%) reperfusion after endovascular treatment without mechanically amendable target-occlusion (as per definition by the interventionalist).
  3. Any emboli to new 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)
* Any severe bleeding within the past 6 months, which would prevent administration of intravenous thrombolysis in clinical routine Major surgery in the past 2 months with severe risk of bleeding, which would prevent administration of intravenous thrombolysis in clinical routine
* Intake of Vitamin K antagonists with INR \&gt;1.7
* Platelets \&lt; 50,000
* Non-controlled hypertension (defined as SBP \&gt;185 mmHg or DBP \&gt;110 mmHg refractory to treatment)
* Active dyspeptic ulcer
* Known arterial aneurysm
* Known neoplasms with risk of bleeding
* Severe liver fibrosis or portal hypertension
* Acute pericarditis
* Acute endocarditis
* Acute pancreatitis
* Known allergy to TNK or Gentamicin or other additives/auxiliaries (Polysorbatum 20, L-Argininum, Acidum phosphoricum)
* Known Renal failure either as defined by a serum creatinine \&gt; 3.0 mg/dl (or 265.2 μmol/l) or glomerular Filtration Rate \[GFR\] \&lt; 30 or as subject who required hemodialysis/peritoneal dialysis
* Radiological confirmed evidence of mass effect or intracranial tumor (except small meningioma)
* Radiological confirmed evidence of cerebral vasculitis
* Calcified thrombi
* Pregnancy or lactating women

Primary outcomes:
measure: Early reperfusion of the residual intracranial occlusion(s)
timeFrame: 25 minutes after randomization
measure: Late reperfusion of the residual intracranial occlusion(s)
timeFrame: 24 hours ±6 hours
Secondary outcomes:
measure: Degree of disability or dependence assessed by the modified ranking scale (mRS) (shift analysis)
timeFrame: 90 days+/-15 days
measure: Normalized change in National Institute of Health Score Scale (NIHSS)
timeFrame: 24 hours +/- 6 hours post-randomization
measure: Change in National Institute of Health Score Scale (NIHSS)
timeFrame: 90 days +/- 15 days post-randomization
measure: Quality of life as assessed by the EuroQol 5D-3L (EQ-5D-3L)
timeFrame: 90 days +/- 15 days
measure: All-cause mortality
timeFrame: 90 days
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LKH-Universitätsklinikum Graz
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Linz
country: Austria
facility: Kepler Universitätsklinikum GmbH
city: Salzburg
country: Austria
facility: Christian-Doppler-Klinik Salzburg
city: Anderlecht
country: Belgium
facility: Hôpital universitaires de Bruxelles
city: Brugge
country: Belgium
facility: AZ Sint Jan Brugge AV
city: Brussel
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Gasthuisberg Leuven
city: Liège
country: Belgium
facility: Clinique CHC MontLégia
city: Helsinki
country: Finland
facility: University Hospital Helsinki
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
city: Erfurt
country: Germany
facility: Helios Klinikum Erfurt
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Asklepios Klinik Altona
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Kiel
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg A. ö. R.
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: München
country: Germany
facility: Klinikum der Universität München
city: München
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: Universitätsspital Bern
city: Genève
country: Switzerland
facility: Hôpitaux universitaires de Genève
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: St.Gallen
country: Switzerland
facility: Kantonsspital St.Gallen
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: NCTU
name: Urs Fischer, PhD
role: STUDY_DIRECTOR
References: