Stereotactic Thrombolysis With Tenecteplase for Supratentorial Intracerebral Hemorrhage

NCT ID: NCT07208097

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 768 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-25
• Study Completion Date: 2028-06-30

Brief Summary

This is an phase III prospective, multi-center, open-label, randomized controlled trial (RCT) with blinded endpoint assessment. It plans to enroll 768 subjects with spontaneous supratentorial intracerebral hemorrhage, who will be randomly assigned in a 1:1 ratio to the investigational arm (stereotactic minimally invasive puncture for intracerebral hemorrhage combined with TNK liquefaction drainage, single TNK dose of 0.5mg per time or the standard medical treatment group.

Detailed Description

Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease with an incidence rate of 60-80 cases per 100,000 population annually, accounting for approximately 10%-20% of all strokes. Early mortality in ICH patients can reach 30%-40%, and the disability rate remains high in later stages, with roughly two-thirds of patients ultimately dying or becoming disabled.

Brain injury caused by ICH can be categorized into primary and secondary damage. Primary injury results from direct trauma to white matter tracts, the blood-brain barrier, and hematoma mass effect immediately following bleeding. Secondary injury arises from mechanisms such as inflammation, blood-brain barrier disruption, cerebral edema, perihematomal edema, cytotoxicity, and oxidative stress, leading to neurological deficits. Clinical studies have confirmed that hematoma removal reduces mortality in ICH patients and may improve neurological outcomes. Minimally invasive hematoma evacuation combined with thrombolytics like rt-PA or urokinase has shown safety and reduced mortality but fails to improve functional outcomes. Post-hoc analyses reveal variable efficacy of rt-PA in liquefying hematomas, with incomplete evacuation and residual clots in some patients. Theoretically, faster and more efficient hematoma liquefaction could enhance clinical outcomes. Tenecteplase has demonstrated superior efficacy, rapid action, and safety in ischemic stroke compared to rt-PA, suggesting potential benefits for ICH hematoma clearance.

To determine the efficacy and safety of local injection of TNK via stereotactic minimally invasive puncture surgery for the treatment of acute spontaneous supratentorial intracerebral hemorrhage (ICH). This is a national, multicenter clinical trial spontaneously organized and designed by the investigators. It employs a Phase III prospective, multicenter, open-label, randomized, standard medical therapy parallel-controlled design, with blinded endpoint assessors. Subjects meeting the inclusion and exclusion criteria will be enrolled according to randomization principles. Investigators blinded to group allocation will conduct assessments and evaluations at various time points during the follow-up period for enrolled patients' post-randomization, either through face-to-face visits or telephone follow-ups.

Conditions

Intracerebral Haemorrhage; Minimally Invasive Treatment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MIS+TNK

In this group, patients receive standard medical treatment plus stereotactic minimally invasive aspiration combined with tenecteplase. The single dose of tenecteplase is 0.5mg.

Group Type: EXPERIMENTAL

Stereotactic thrombolysis with Tenecteplase

Intervention Type: PROCEDURE

Stereotactic thrombolysis with Tenecteplase for ICH is a minimally invasive method for evacuation hematoma. The hematoma puncture target is identified via CT imaging before surgery. After local anesthesia and sedation, stereotactic minimally invasive surgery is performed with the Leksell stereotactic frame. A postoperative CT scan is immediately conducted to confirm the absence of intracranial rebleeding before administering tenecteplase into the hematoma. Tenecteplase is fully diluted in 2 mL of saline and injected into the hematoma cavity via an irrigation catheter. The drainage tube is clamped for 1 hour before opening (early opening is permitted if necessary). The single dose of TNK is 0.5 mg and can be administered with a maximum of 2 dose in every 24 hours. The target hematoma clearance criteria is: residual hematoma volume ≤10 mL or ≤20% of the initial volume.

Standard medical treatment

Patients randomized to the control group will receive standard medical management according to the 2022 AHA/ASA Guideline for the Management of Spontaneous Intracerebral Hemorrhage.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Stereotactic thrombolysis with Tenecteplase

Stereotactic thrombolysis with Tenecteplase for ICH is a minimally invasive method for evacuation hematoma. The hematoma puncture target is identified via CT imaging before surgery. After local anesthesia and sedation, stereotactic minimally invasive surgery is performed with the Leksell stereotactic frame. A postoperative CT scan is immediately conducted to confirm the absence of intracranial rebleeding before administering tenecteplase into the hematoma. Tenecteplase is fully diluted in 2 mL of saline and injected into the hematoma cavity via an irrigation catheter. The drainage tube is clamped for 1 hour before opening (early opening is permitted if necessary). The single dose of TNK is 0.5 mg and can be administered with a maximum of 2 dose in every 24 hours. The target hematoma clearance criteria is: residual hematoma volume ≤10 mL or ≤20% of the initial volume.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. . Age 18 to 80 years, any gender.

2. . Clinically confirmed acute spontaneous supratentorial intracerebral hemorrhage (ICH), with diagnostic CT completed within 24 hours of symptom onset (for patients with unknown time of onset or wake-up stroke, the time from the last known well to symptom detection is used as the presumed onset time).

3. . CT-confirmed supratentorial ICH with hematoma volume calculated by ABC/2 method between 25 mL and 60 mL (inclusive).

4. . National Institutes of Health Stroke Scale (NIHSS) score ≥ 6.

5. .Glasgow Coma Scale (GCS) score between 9 and 14 (inclusive).

6. . Pre-stroke modified Rankin Scale (mRS) score ≤ 1.

7. . Good compliance, with written informed consent provided by the patient and/or legal guardian, and ability to adhere to the scheduled follow-up visits.

Exclusion Criteria

1. . Brainstem or cerebellar hemorrhage; or thalamic hemorrhage with significant midbrain shift accompanied by third nerve palsy or unreactive dilated pupils.

2. . Irreversible brainstem dysfunction (bilateral fixed, dilated pupils and decerebrate posturing).

3. . Secondary ICH caused by: head trauma, arteriovenous malformation (AVM), moyamoya disease, intracranial aneurysm, coagulation disorders (hereditary or acquired hemorrhagic diathesis, hemophilia, coagulation factor deficiency, leukemia, etc.), hemorrhagic transformation of cerebral infarction, or tumor; multiple intracranial hemorrhages, subarachnoid hemorrhage (SAH), primary intraventricular hemorrhage, drug-induced hemorrhagic stroke, subdural hemorrhage, epidural hemorrhage.

4. . Significant abnormalities in the following laboratory parameters:(1)International normalized ratio (INR) > 1.4; any irreversible coagulopathy or known coagulation disorder that cannot be corrected with procoagulants to maintain INR ≤ 1.4. (2) Severe hepatic insufficiency: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN). (3) Severe renal insufficiency: estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m². (4)Hemoglobin < 90 g/L.5）Platelet count < 100 × 10⁹/L.

5. . History of malignancy, autoimmune diseases (including but not limited to systemic lupus erythematosus, systemic vasculitis), hemorrhagic diathesis (including various hereditary and acquired bleeding disorders), malignant arrhythmias, cardiac insufficiency (B-type natriuretic peptide [BNP] ≥ 1000 pg/mL or left ventricular ejection fraction [LVEF] ≤ 40%), acute myocardial infarction, acute or severe infectious diseases (e.g., intracranial infection, severe pneumonia, sepsis), or any other severe concurrent illness that may exacerbate the condition or interfere with efficacy assessment.

6. . Known high risk of thromboembolism, including: presence of a mechanical heart valve prosthesis, history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis. (Note: Atrial fibrillation without mitral stenosis is permitted).

7. . Myocardial infarction within 30 days prior to randomization.

8. .Use of anticoagulants (e.g., warfarin, dabigatran, rivaroxaban, apixaban) within 1 week prior to symptom onset.

9. . History of internal bleeding (e.g., gastrointestinal bleeding, genitourinary bleeding, retroperitoneal bleeding) within 3 months prior to randomization.

10. . Major surgery or vascular puncture (e.g., venesection, arterial puncture) within 3 months prior to randomization.

11. . History of significant head trauma or severe stroke within 3 months prior to randomization.

12. . History of intracerebral hemorrhage within 1 year prior to randomization.

13. . Indications for craniotomy: (1) Progressive impairment of consciousness; (2)Preoperative signs of brain herniation (e.g., foramen magnum herniation, tentorial herniation) posing a life-threatening condition.

14. . Intraventricular hemorrhage (IVH) or ICH with rupture into the ventricle causing intraventricular cast formation and/or hydrocephalus anticipated to require external ventricular drainage (EVD).

15. . Patient or family requests craniotomy or neuroendoscopic surgery for hematoma evacuation.

16. . Pre-randomization decision by patient/family for Do-Not-Resuscitate (DNR) or Do-Not-Intubate (DNI) orders regarding life-sustaining measures.

17. . Known hypersensitivity or intolerance to TNK.

18. . Pregnancy (positive urine pregnancy test) in women of childbearing potential.

19. . Concurrent participation in another investigational drug or device study.

20. . History of drug or alcohol abuse/dependence, severe dementia, or psychiatric disorder prior to randomization, anticipated to result in poor compliance and inability to complete follow-up.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tongji Hospital

OTHER

Sponsor Role: lead

Responsible Party

Tang Zhouping

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Suzhou First People's Hospital

Suzhou, Anhui, China

Site Status: RECRUITING

Guizhou Medical University Affiliated Hospital

Guiyang, Guizhou, China

Site Status: ACTIVE_NOT_RECRUITING

Countries

China

Central Contacts

Pan Chao, MD, PhD

Role: CONTACT

ddjtzp@163.com; punctualpc@163.com

86-027-83663337

Facility Contacts

Bin Liu

Role: primary

2217043918@qq.com

+8615255701930

Other Identifiers

TJ-IRB202511008

Identifier Type: -

Identifier Source: org_study_id