Intra-arterial Tenecteplase for Acute Medium Vessel Occlusion Stroke
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorBeijing Tiantan Hospital
About this trial
The ANGEL-MeVO-TNK is a multicentered, prospective, randomized, open label, blinded endpoint (PROBE) phase III trial. A total of 488 AIS patients (age ≥18 years) with acute MeVO-AIS (occlusion of the M2/M3, the A1/A2/A3, the P1/P2/P3, and with baseline NIHSS score \>5 or disabling stroke with NIHSS score 3-5 \[such as neurological deficits in motor strength, language, vision, etc\]), will be enrolled. Patients fulfilling all the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into the IA TNK group or the control group after offering informed content.
* The IA TNK group：1) If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) .
2\) If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes. * The control group will be given standard medical management.
The study consists of four visits including the day of randomization, 48±12 hours after randomization, and 90±7 days after randomization. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment neurological function rating scale will be recorded during the program.
The primary outcome is the modified Rankin Scale (mRS) score of 0 to 1 at 90±7 days after onset. The primary safety outcome is the incidence of sICH within 48±12 hours after randomization (ECASS III).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years;
Pre-stroke mRS 0-1;
Within 24 h from symptom onset;
Baseline National Institutes of Health Stroke Scale (NIHSS) score >5 or baseline NIHSS 3-5 with disabling deficit (e.g., loss of hand function, aphasia, hemianopia);
Disqualifiers
Acute intracranial hemorrhage;
ASPECT ≤5;
MeVO secondary to spontaneous fragmentation and distal migration of thrombus from an acute large vessel occlusion, or occurring after intravenous thrombolysis (IVT), intra-arterial thrombolysis, or endovascular thrombectomy;
Contraindication to TNK;
Trial design
Design model
Parallel
Treatments tested in this trial
Intra-arterial Tenecteplase
Procedure/Surgery1. If the patient has not received IVT, IA TNK will be administered as a slow, continuous infusion for super-selective contact thrombolysis in a stepwise manner: an initial dose of 0.0625 mg/kg with a duration of 15 minutes. A repeat angiographic assessment will then be performed; if recanalization is not achieved, an additional dose of 0.0625 mg/kg will be administered over a further 15 minutes (maximum dose 12.5 mg) . 2. If the patient has received IVT, intra-arterial TNK will be administered as a slow infusion for super-selective contact thrombolysis at a dose of 0.0625 mg/kg (maximum dose 6.25 mg) with a duration of 15 minutes.
standard medical management
DrugPatients will receive standard medical management as recommended by current guidelines# #《Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke (2023)》and《Chinese Guidelines for Secondary Prevention of Ischemic Stroke and Transient Ischemic Attack (2022)》
Treatment groups
488 Participants
are divided into 2 treatment groupsGroup A: IA TNK groupExperimental treatment 1 intervention
Group B: Control group (Standard medical management group)Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
mRS score of 0 to 1 at 90±7 days after onset
The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death.
Time frame
90±7 days after onset2
symptomatic intracerebral hemorrhage within 48±12 hours after randomization
symptomatic intracerebral hemorrhage (sICH) within 48±12 hours after randomization (ECASS III criteria)
Time frame
48±12 hours after randomizationSecondary outcomes
1
Ordinal mRS score at 90±7 days after onset
The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death.
Time frame
90±7 days after onset2
mRS score 0 to 2 at 90±7 days after onset
The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death.
Time frame
90±7 days after onset3
mRS score 0 to 3 at 90±7 days after onset
The modified Rankin scale is a measure of disability, with scores ranging from 0 (no symptoms) to 6 (death), with 0 indicating no symptoms at all; 1 indicating no significant disability despite symptoms: able to carry out all usual duties and activities, 2 indicating slight disability: unable to carry out all previous activities but able to look after own affairs without assistance; 3 indicating moderate disability: requiring some help, but able to walk without assistance; 4 indicating moderately severe disability: unable to walk without assistance, and unable to attend to own bodily needs without assistance; 5 indicating severe disability: bedridden, incontinent, and requiring constant nursing care and attention; and 6 indicating death.
Time frame
90±7 days after onset4
Number of Participants with Recanalization of the target occluded artery within 48 ± 12 hours after randomization
defined as an Arterial Occlusive Lesion \[AOL\] score of 2-3 on CTA or MRA. The Arterial Occlusive Lesion (AOL) Score is a standardized, angiographic (imaging-based) classification system used to quantify the degree of recanalization (blood flow restoration) in an occluded artery following an endovascular thrombectomy procedure for acute ischemic stroke. Score Range: 0 to 3 (ordinal). A higher score indicates a greater degree of successful mechanical recanalization of the target artery.
Time frame
48 ± 12 hours after randomizationSponsors and contacts
Click on the lead sponsor to view all of their trials.
Beijing Tiantan Hospital
Lead sponsor
Boehringer Ingelheim
Collaborator
Source ClinicalTrials.gov