rhTNK-tPA Thrombolytic Removal of Intraventricular Hemorrhage

Launched by BEIJING TIANTAN HOSPITAL · Feb 3, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for patients who have experienced intraventricular hemorrhage, which is bleeding inside the brain's ventricles. The researchers want to find out if a medication called rhTNK-tPA is safe and what the best dose is to help dissolve clots caused by this bleeding. To do this, they will use a special method to place a drain in the brain to help monitor the situation.

To be eligible for this trial, participants need to be between 18 and 80 years old, have had symptoms of bleeding within the last 24 hours, and have specific types of bleeding in the brain that meet certain criteria. Patients will receive close monitoring and care during the study. It's important to know that this is the first phase of research, so they are gathering initial information about safety and effectiveness. If you or a loved one are considering participation, you will need to meet certain health requirements, and the medical team will provide detailed information about the process and what to expect.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Age 18-80 years.
• • 2. Symptom onset within 24 hours prior to diagnostic CT scan. Patients with unknown onset time should be excluded. For patients with symptoms occurring during sleep, the time of symptom onset should be considered as the last time the patient was awake and asymptomatic.
• • 3. Spontaneous intracerebral hemorrhage (ICH) ≤ 30 ml，with intraventricular hemorrhage (IVH) \>20 ml obstructing the third and/or fourth ventricles.
• • 4. All patients must have an external ventricular drain (EVD) placed prior to enrollment: The EVD should be accurately positioned into the largest cerebrospinal fluid (CSF) pool or the least bloody site in the lateral ventricle using robotic stereotactic guidance.
• • 5. A stability CT scan performed ≥ 6 hours after EVD placement must confirm ICH clot stability: The ICH volume change should be ≤ 5 ml compared to the previous CT scan. If the stability CT scan shows a difference \> 5 ml, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a hematoma enlargement ≤ 5 ml and the ICH volume remains ≤ 35 ml, the patient is eligible.
• • 6. IVH clot stability: The width of the lateral ventricle most affected by the clot must not increase by \> 2 mm. If the stability CT scan shows a difference \> 2 mm, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a change ≤ 2 mm, the patient is eligible.
• • 7. Catheter tract bleeding on the stability CT scan must be ≤ 5 ml. If any CT slice shows catheter tract bleeding \> 5 ml, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a change ≤ 5 ml and the total hematoma volume along the tract is ≤ 10 ml, the patient is eligible.
• • 8. On the stability CT scan, the third and/or fourth ventricles must be occluded with blood.
• • 9. Primary IVH (ICH = 0) is eligible.
• • 10. Sustained systolic blood pressure (SBP) \< 180 mmHg for at least 6 hours prior to enrollment. (Patients do not need to meet the SBP criteria throughout the screening period, but vital signs should remain stable during the enrollment window).
• • 11. No intraventricular thrombolytic treatment within 12 hours of symptom onset.
• • 12. Enrollment must be completed within 72 hours of the diagnostic CT scan. (The 72-hour limit may be extended with PI approval for reasons such as hematoma stability, INR stability, or other valid justifications).
• • 13. Pre-morbid modified Rankin Scale (mRS) score of 0 or 1.
• Exclusion Criteria:
• • 1. Hemorrhage caused by aneurysms, arteriovenous malformations (AVM), tumors, or other identifiable causes. If the cause of ICH is unknown, CTA, DSA, or other definitive imaging must be performed during screening to rule out these causes. If imaging is negative, the patient is eligible.
• • 2. Presence of choroid plexus vascular malformation or Moyamoya disease.
• • 3. Hypercoagulable state or coagulopathy. Patients requiring long-term anticoagulation are excluded. Reversal of anticoagulation is permitted if long-term anticoagulation is not required.
• • 4. Use of anticoagulants (e.g., dabigatran, apixaban, rivaroxaban) or antiplatelet agents (e.g., tirofiban, ticagrelor, cilostazol, clopidogrel) within one week prior to symptom onset (aspirin is allowed).
• • 5. Platelet count \< 100,000 or INR \> 1.4.
• • 6. Pregnancy (positive serum or urine pregnancy test).
• • 7. Infratentorial hemorrhage.
• • 8. Thalamic hemorrhage with significant midbrain extension, third nerve palsy, or dilated and non-reactive pupils. Other supranuclear gaze abnormalities are not excluded. Posterior fossa or cerebellar hemorrhages are excluded.
• • 9. Subarachnoid hemorrhage (SAH) or any atypical hematoma location or appearance on diagnostic CT scan. Angiography (CTA, DSA, or MRA/MRI) must be performed to rule out other causes. If no source of bleeding is identified, the patient is eligible. Cortical SAH secondary to clot lysis is eligible.
• • 10. Unstable ICH/IVH with ongoing hematoma enlargement.
• • 11. Indications for craniotomy: ① Progressive decline in consciousness; ② Signs of brain herniation; ③ Hematoma located \< 1 cm from the cortical surface.
• • 12. Ongoing internal bleeding involving retroperitoneal, gastrointestinal, genitourinary, or respiratory tracts. Patients with prior bleeding that is clinically stable for ≥ 12 hours and without coagulopathy or bleeding disorders are eligible.
• • 13. Multifocal superficial bleeding at multiple vascular puncture or access sites (e.g., venipuncture, arterial puncture) or recent surgical sites.
• • 14. Any condition that, in the investigator's opinion, poses a significant risk to the patient or makes the patient unsuitable for the study.
• • 15. Planned or concurrent participation in another interventional clinical trial. Participation in observational, natural history, or epidemiological studies without intervention is allowed.
• • 16. Inability to obtain informed consent from the patient or legal representative.