Using a specific medication to improve outcomes after stroke treatment

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)

This study is testing if a specific medication can help improve recovery for stroke patients who have already had a procedure to remove a blood clot.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 256 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tiantan Hospital (other)
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT05624190 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the effectiveness of intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis in enhancing neurological outcomes for patients who have undergone successful mechanical thrombectomy for acute large vessel occlusion. Participants will be randomly assigned to either receive the rhTNK-tPA treatment along with best medical management or to a control group receiving only best medical management. The trial focuses on patients treated within a specific time frame after symptom onset, ensuring a targeted approach to acute ischemic stroke management.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 years old with a confirmed large vessel occlusion who have undergone successful mechanical thrombectomy within 4.5 to 24 hours of symptom onset.

Not a fit: Patients who have received intravenous thrombolysis prior to admission or have severe pre-existing disabilities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recovery outcomes for patients suffering from acute ischemic strokes.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in improving outcomes for stroke patients, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

Clinical Inclusion Criteria:

1. Age \>18 years;
2. NIHSS ≥2;
3. 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);
4. Pre-stroke mRS score 0-1;
5. Signed informed consent from patient or their health care proxy.

Neuroimaging Inclusion Criteria:

1. CTA/MRA proven intracranial artery occlusion: Intracranial Internal Carotid Artery (ICA)、M1 of Middle cerebral artery (MCA)、dominant M2 of MCA;
2. ASPECTS ≥6 on non-contrast CT (NCCT) scan or DWI MRI;
3. CT perfusion or MR perfusion: ischemic infarct core \<70ml, mismatch ratio≥1.2, mismatch volume ≥15ml;
4. 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.

Exclusion Criteria:

Clinical Exclusion Criteria:

1. IV thrombolysis used on admission;
2. Contraindications to intravenous thrombolysis;
3. Balloon angioplasty, permanent stenting and other situations during the endovascular procedure that require antiplatelet therapy or anticoagulant within the first 24h;
4. IV heparin (heparinized saline allowed);
5. Females who are pregnant, or those of child-bearing potential with positive urine or serum beta Human Chorionic Gonadotropin (HCG) test;
6. Brain tumor (with mass effect);
7. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency
8. Known coagulopathy, INR\>1.7 or use of novel anticoagulants \< 48h from symptom onset
9. Platelets \< 50\*109/L;
10. Suspicion of septic emboli or endocarditis
11. Renal Failure as defined by a serum creatinine \> 2.5 mg/dl (or 220μmol/l) or glomerular Filtration Rate \[GFR\] \< 30ml/min;
12. Patient who requires hemodialysis or peritoneal dialysis, or who has a contraindication to angiogram for whatever reason;
13. Suspicion of aortic dissection;
14. Parenchymal organ surgery and biopsy were performed in the past one month;
15. Any active bleeding or recent bleeding (gastrointestinal bleeding, urinary bleeding, etc.) in the past 1 month;
16. History of life-threatening allergy (more than rash) to contrast medium;
17. SBP \>185 mmHg or DBP \>110 mmHg refractory to treatment;
18. Serious, advanced, terminal illness with anticipated life expectancy \< 6 months;
19. Participation in another randomized clinical trial that could confound the evaluation of the study;
20. 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

1. Midline shift or herniation, mass effect with effacement of the ventricles
2. Evidence of acute intracranial hemorrhage on CT/MRI
3. Acute bilateral strokes or multiple intracranial vessel occlusions
4. Isolated extracranial ICA occlusion or tandem carotid / MCA occlusion
5. Dissection of occluded artery on DSA after thrombectomy

Where this trial is running

Beijing, Beijing

• Beijing Tiantan Hospital, Capital Medical University — Beijing, Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Xiaochuan Huo, Dr.

Conditions: Ischemic Stroke, Acute