Using rhTNK-tPA to treat intraventricular hemorrhage

A Phase I Pilot Clinical Trial of Dose Escalation With Stereotactic-Guided Intraventricular Thrombolysis Using Tenecteplase (rhTNK-tPA) for Intraventricular Hemorrhage.

This study is testing a new treatment using rhTNK-tPA for people with bleeding in the brain to see if it can help them recover better and improve their chances of survival.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (Academic / other)
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06814964 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the safety and optimal dosing of rhTNK-tPA for the treatment of intraventricular hemorrhage (IVH) using stereotactic guidance for the placement of an external ventricular drain. Patients with spontaneous intracerebral hemorrhage and significant IVH will receive varying doses of rhTNK-tPA to assess its effectiveness in clot lysis. The study seeks to improve survival rates and functional outcomes by alleviating hydrocephalus and reducing neurotoxicity associated with IVH. The research builds on previous findings that suggest thrombolytic therapy can positively impact patient outcomes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with spontaneous intracerebral hemorrhage and significant intraventricular hemorrhage requiring external ventricular drainage.

Not a fit: Patients with known onset times exceeding 24 hours or those with ICH volumes greater than 30 ml may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and functional recovery for patients suffering from intraventricular hemorrhage.

How similar studies have performed: Previous studies have shown promise with thrombolytic therapies for IVH, but this specific approach using rhTNK-tPA is novel.

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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Tiantan Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yong Cao — Beijing Tiantan Hospital
• Study coordinator: Yong Cao

Conditions Intraventricular Hemorrhage; intraventricular hemorrhage; Stereotactic puncture therapy; rhTNK-tPA