Ischemic Stroke, AcutePhase 4ANGEL-TNKNCT05624190
Intra-arterial Recombinant Human TNK Tissue-type Plasminogen Activator (rhTNK-tPA) Thrombolysis for Acute Large Vascular Occlusion After Successful Mechanical Thrombectomy Recanalization
A Phase 4 study testing Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) and Best Medical Management in people with Ischemic Stroke, Acute, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke, Acute
- What is being tested?
- Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) and Best Medical Management
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 256 participants
- Where
- 1 siteChina
- Study dates
- 16 Feb 2023to Jul 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical Inclusion Criteria:
- Age >18 years;
- NIHSS ≥2;
- Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW);
- Pre-stroke mRS score 0-1;
- Signed informed consent from patient or their health care proxy.
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- Neuroimaging Inclusion Criteria:
- CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA;
- ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI;
- CT perfusion or MR perfusion: ischemic infarct core <70ml, mismatch ratio≥1.2, mismatch volume ≥15ml;
- Treated with MT resulting in an eTICI score 2b50-3 at end of the procedure. Patients with an eTICI score 2b50-3 on the diagnostic cerebral angiography before the onset of MT are also eligible for the study.
Who cannot join
- Clinical Exclusion Criteria:
- IV thrombolysis used on admission;
- Contraindications to intravenous thrombolysis;
- Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;
- IV heparin (heparinized saline allowed);
- Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
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- Brain tumor (with mass effect);
- Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
- Known coagulopathy, INR>1.7 or use of novel anticoagulants < 48h from symptom onset
- Platelets < 50*109/L;
- Suspicion of septic emboli or endocarditis
- Renal Failure as defined by a serum creatinine > 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate [GFR] < 30ml/min;
- Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason;
- Suspicion of aortic dissection;
- Parenchymal organ surgery and biopsy were performed in the past one month;
- Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month;
- History of life-threatening allergy (more than rash) to contrast medium;
- SBP >185 mmHg or DBP >110 mmHg refractory to treatment;
- Serious, advanced, terminal illness with anticipated life expectancy < 6 months;
- Participation in another randomized clinical trial that could confound the evaluation of the study;
- Other circumstances that the investigator considers inappropriate for participation or may pose a significant risk to patients (e.g. inability to understand and/or comply with study procedures and/or follow-up due to mental disorders, cognitive or mood disorders).
- Specific Neuroimaging Exclusion Criteria
- Midline shift or herniation, mass effect with effacement of the ventricles
- Evidence of acute intracranial hemorrhage on CT/MRI
- Acute bilateral strokes or multiple intracranial vessel occlusions
- Isolated extracranial ICA occlusion or tandem carotid / MCA occlusion
- Dissection of occluded artery on DSA after thrombectomy
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100070
Zhongrong Miao
About this study
Official title: Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator rhTNK-tPA) Thrombolysis for Acute Large Vessel Occlusion After Successful Mechanical Thrombectomy Recanalization -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial (ANGEL-TNK)
The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Participants enrolled will be randomly assigned to study or control arm with a 1:1ratio. Study group will receive IA rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus best medical management, and control receive best medical management alone.
- Conditions
- Ischemic Stroke, Acute
- Being tested
- Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA), Best Medical Management
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)Drug
Also called IA rhTNK-tPA
The administration of rhTNK-tPA will be infused constant and slowly over 15min (0.125 mg/kg, Max 12.5mg) through a microcatheter.
Best Medical ManagementOther
Best Medical Management
| Study group | Role | What they receive |
|---|---|---|
| TNK group | Experimental | Patients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization Receives: Drug: Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA); Other: Best Medical Management |
| control group | Active comparator | Patients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization Receives: Other: Best Medical Management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of excellent outcome
Rate of 90 (±7) day modified Rankin scale (mRS) 0-1
Measured: 90±7 days after randomization
Secondary outcomes (10)
Rate of sICH (Heidelberg Bleeding Classification)
Rate of sICH (Heidelberg Bleeding Classification)
Measured: within 48 hours after randomization
Volume of Tmax>6s
Measured: 24 hours (±12 hours) after randomization
Infarct core volume change from baseline
Infarct core volume change from baseline, assessed with NCCT at 7 days (±1 day) after randomization/at discharge or with MRI at 36 hours (±12 hours)
Measured: 7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization
mRS (shift analysis)
mRS (shift analysis)
Measured: 90 days (±7 days) after randomization
Rate of good outcome
Rate of mRS 0-2
Measured: 90 days (±7 days) after randomization
Rate of mRS 0-3
Rate of mRS 0-3
Measured: 90 days (±7 days) after randomization
NIHSS 0-1 or decrease ≥10 from baseline NIHSS
NIHSS 0-1 or decrease ≥10 from baseline NIHSS
Measured: 36 hours (±12hours) after randomization
EQ-5D-5L score
EQ-5D-5L score
Measured: 90 days (±7 days) after randomization
All-caused mortality
All-caused mortality
Measured: 90 days (±7 days) after randomization
Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
Measured: within 48 hours after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2022
- Study start16 Feb 2023
- Primary completionJul 2024 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Ischemic Stroke, AcuteStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 256 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhongrong Miao, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05624190
- Sponsor's protocol ID
- HX-A-2022041
- Acronym
- ANGEL-TNK
- Status last verified
- Mar 2024
- First submitted
- 14 Nov 2022
- Last updated
- 19 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Zhang X, Tong X, Luo G, Song L, Sun D, Chen W, Yao X, Zhou Q, Li S, Miao Z, Huo X; ANGEL-TNK Investigators. Relationship Between the eTICI Score Before Randomization and 90-Day Outcome: A Post Hoc Analysis of ANGEL-TNK Trial. Stroke. 2026 Oct 29. doi: 10.1161/STROKEAHA.126.057260. Online ahead of print.
PubMed 42953960Miao Z, Luo G, Song L, Sun D, Chen W, Yao X, Pan Y, Liu Y, Yuan G, Wen C, Wei M, Cai X, Yang Q, Zhou Z, Chang M, Nan G, Wang J, Xiang G, Zhou L, Gao W, Zhang H, Hao J, Xu C, Sun Y, Yi T, Feng G, Han H, Gao F, Ma N, Mo D, Sun X, Deng Y, Tong X, Li X, Jia B, Wang B, He Z, Yang M, Zhao X, Zhang X, Zhang L, Li S, Tong X, Jing J, Xiong Y, Liu T, Li Z, Ren Z, Wang Y, Liebeskind DS, Jovin TG, Nguyen TN, Wang Y, Liu L, Yan B, Huo X; ANGEL-TNK Investigators. Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial. JAMA. 2025 Aug 19;334(7):582-591. doi: 10.1001/jama.2025.10800.
PubMed 40616323Huo X, Luo G, Sun D, Nguyen T, Abdalkader M, Chen W, Yao X, Yuan G, Yi T, Han H, Pan Y, Jovin TG, Liebeskind DS, Liu L, Zhao X, Ren Z, Wang Y, Wang Y, Yan B, Miao Z. Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial. Stroke Vasc Neurol. 2025 Aug 26;10(4):508-513. doi: 10.1136/svn-2024-003318.
PubMed 39357896
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intra-arterial Recombinant Human Tenecteplase Tissue-type Plasminogen Activator rhTNK-tPA) Thrombolysis for Acute Large Vessel Occlusion After Successful Mechanical Thrombectomy Recanalization -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial (ANGEL-TNK)
- ClinicalTrials.gov ID
- NCT05624190
- Acronym / sponsor ID
- ANGEL-TNK / HX-A-2022041
- Conditions
- Ischemic Stroke, Acute
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 256 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 16 Feb 2023 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 22 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate whether intra-arterial (IA) rhTNK-tPA thrombolysis can improve neurological outcomes in acute large vessel occlusion patients after successful mechanical thrombectomy (MT) recanalization between 4.5- 24 hours from symptom onset. Participants enrolled will be randomly assigned to study or control arm with a 1:1ratio. Study group will receive IA rhTNK-tPA thrombolysis (0.125 mg/kg, Max 12.5mg) plus best medical management, and control receive best medical management alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TNK group | Experimental | Drug: Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA), Other: Best Medical ManagementPatients of this group will receive IA rhTNK-tPA plus Best Medical Management (BMM) after successful mechanical thrombectomy (MT) recanalization |
| control group | Active comparator | Other: Best Medical ManagementPatients of this group will receive Best Medical Management (BMM) alone after successful mechanical thrombectomy (MT) recanalization |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age >18 years;
- NIHSS ≥2;
- Onset of symptoms to baseline CT imaging time: 4.5 to 24 hours, including wake-up stroke and unwitnessed stroke; Time of onset of symptoms is defined as "last known well" (LKW);
- Pre-stroke mRS score 0-1;
- Signed informed consent from patient or their health care proxy.
Key exclusion criteria (27 listed)
- IV thrombolysis used on admission;
- Contraindications to intravenous thrombolysis;
- Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;
- IV heparin (heparinized saline allowed);
- Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA)Also: IA rhTNK-tPAThe administration of rhTNK-tPA will be infused constant and slowly over 15min (0.125 mg/kg, Max 12.5mg) through a microcatheter. | Drug | TNK group |
| Best Medical ManagementBest Medical Management | Other | TNK group, control group |
Primary outcome
Rate of excellent outcome
Time frame: 90±7 days after randomization
Rate of 90 (±7) day modified Rankin scale (mRS) 0-1
10 secondary outcomes
Rate of sICH (Heidelberg Bleeding Classification)
Time frame: within 48 hours after randomization
Volume of Tmax>6s
Time frame: 24 hours (±12 hours) after randomization
Infarct core volume change from baseline
Time frame: 7 days (±1 day) after randomization/at discharge or at 36 hours (±12 hours) after randomization
mRS (shift analysis)
Time frame: 90 days (±7 days) after randomization
Rate of good outcome
Time frame: 90 days (±7 days) after randomization
Rate of mRS 0-3
Time frame: 90 days (±7 days) after randomization
NIHSS 0-1 or decrease ≥10 from baseline NIHSS
Time frame: 36 hours (±12hours) after randomization
EQ-5D-5L score
Time frame: 90 days (±7 days) after randomization
All-caused mortality
Time frame: 90 days (±7 days) after randomization
Rate of any intracranial hemorrhage (Heidelberg Bleeding Classification)
Time frame: within 48 hours after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2024.
- Derived from this study: PubMed 42953960Zhang X, Tong X, Luo G, Song L, Sun D, Chen W, Yao X, Zhou Q, Li S, Miao Z, Huo X; ANGEL-TNK Investigators. Relationship Between the eTICI Score Before Randomization and 90-Day Outcome: A Post Hoc Analysis of ANGEL-TNK Trial. Stroke. 2026 Oct 29. doi: 10.1161/STROKEAHA.126.057260. Online ahead of print.
- Derived from this study: PubMed 40616323Miao Z, Luo G, Song L, Sun D, Chen W, Yao X, Pan Y, Liu Y, Yuan G, Wen C, Wei M, Cai X, Yang Q, Zhou Z, Chang M, Nan G, Wang J, Xiang G, Zhou L, Gao W, Zhang H, Hao J, Xu C, Sun Y, Yi T, Feng G, Han H, Gao F, Ma N, Mo D, Sun X, Deng Y, Tong X, Li X, Jia B, Wang B, He Z, Yang M, Zhao X, Zhang X, Zhang L, Li S, Tong X, Jing J, Xiong Y, Liu T, Li Z, Ren Z, Wang Y, Liebeskind DS, Jovin TG, Nguyen TN, Wang Y, Liu L, Yan B, Huo X; ANGEL-TNK Investigators. Intra-arterial Tenecteplase for Acute Stroke After Successful Endovascular Therapy: The ANGEL-TNK Randomized Clinical Trial. JAMA. 2025 Aug 19;334(7):582-591. doi: 10.1001/jama.2025.10800.
- Derived from this study: PubMed 39357896Huo X, Luo G, Sun D, Nguyen T, Abdalkader M, Chen W, Yao X, Yuan G, Yi T, Han H, Pan Y, Jovin TG, Liebeskind DS, Liu L, Zhao X, Ren Z, Wang Y, Wang Y, Yan B, Miao Z. Intra-arterial tenecteplase after successful endovascular therapy (ANGEL-TNK): protocol of a multicentre, open-label, blinded end-point, prospective, randomised trial. Stroke Vasc Neurol. 2025 Aug 26;10(4):508-513. doi: 10.1136/svn-2024-003318.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant Human tenecteplase Tissue-type Plasminogen Activator (rhTNK-tPA) and Best Medical Management in people with Ischemic Stroke, Acute, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaochuan Huo, Dr. (+8613716292262, huoxiaochuan@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of excellent outcome (time frame: 90±7 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05624190, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2024.