Neuronavigation-assisted treatment for deep brain bleeding

Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined With Tenecteplase for the Treatment of Acute Spontaneous Deep Intracerebral Hemorrhage(NAS-TNK)： a Randomized, Outcome-blinded, Multi-center Trial

This study is testing a new, less invasive treatment for people with deep brain bleeding to see if it can improve recovery compared to standard care.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 732 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Beijing Tiantan Hospital (other)
• Locations: 1 site (Beijing, China)
• Trial ID: NCT06868511 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of a minimally invasive procedure that combines neuronavigation-assisted stereotactic puncture with tenecteplase thrombolysis for treating acute deep intracerebral hemorrhage. The approach aims to enhance catheter placement accuracy and improve thrombolysis efficiency, potentially leading to better neurological outcomes. Participants will be randomized to receive either the new treatment or standard medical care, with outcomes assessed based on disability and mortality rates. The study is designed to address the current uncertainties surrounding the benefits of this combined technique.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 80 with acute spontaneous deep intracerebral hemorrhage in specific brain regions and a Glasgow Coma Scale score between 5 and 14.

Not a fit: Patients with lobar or subtentorial hemorrhages or those with a Glasgow Coma Scale score below 5 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce disability and mortality rates in patients suffering from deep intracerebral hemorrhage.

How similar studies have performed: Previous studies on minimally invasive techniques for intracerebral hemorrhage have shown promising results, indicating that this approach could be a meaningful advancement in treatment.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years and \<80 years.
2. Symptoms must have manifested within 24 hours prior to the diagnostic CT (dCT) scan. Cases with an indeterminate onset time are excluded. For patients who present symptoms upon sleeping, the last known time they were well should be used.
3. Acute spontaneous deep intracerebral hemorrhage (ICH) occurring in the basal ganglia or thalamus, with a volume between 20-50 mL as measured by ABC/2 method with radiographic imaging (CT, etc.).
4. Glasgow Coma Scale (GCS) score of 5-14.
5. Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth\<5 mL as measured by ABC/2 method).
6. Randomization should occur within 6 to 24 hours after the diagnostic CT.
7. Systolic blood pressure (SBP) less than 180 mmHg maintained for a duration of six hours, documented proximate to the randomization time point.
8. Historical Rankin score of 0 or 1.

Exclusion Criteria:

1. Lobar or subtentorial hemorrhage, including posterior fossa hemorrhage and cerebellar hemorrhage.
2. Stability CT scan done at least 6 hours after diagnostic CT showing clot instability (growth ≥5 mL as measured by ABC/2 method).
3. Intraventricular hemorrhage necessitating intervention to address mass effect or midline shift attributable to trapped ventricle syndrome secondary to intraventricular hemorrhage (IVH)-related casting.
4. Hemorrhage attributable to other cerebrovascular pathologies, including but not limited to ruptured aneurysm, arteriovenous malformation (AVM), vascular anomalies, moyamoya disease, hemorrhagic transformation of an ischemic infarct, or recurrence of a recent hemorrhage within the past year, as diagnosed through radiographic imaging.
5. Patients presenting with an unstable intracranial mass or progressive intracranial compartment syndrome.
6. Thalamic hemorrhages exhibiting evident extension into the midbrain, accompanied by oculomotor nerve palsy or pupils that are dilated and non-reactive. Other supranuclear gaze abnormalities do not constitute exclusion criteria.
7. Irreversible impairment of brainstem function, characterized by bilateral fixed and dilated pupils, extensor motor posturing, and a Glasgow Coma Scale (GCS) score of ≤ 4.
8. Indications for craniotomy in patients include: 1) progressive impairment of consciousness; 2) presence of brain herniation, with signs related to cerebellar tonsil herniation or temporal lobe gyrus herniation; 3) hematoma located within 1 cm of the cortical surface.
9. CT evidence suggesting a high risk of rebleeding, such as spot sign.
10. Platelet count \<100,000/mL; INR \>1.4.
11. Any irreversible coagulation disorders (e.g., hemophilia, von Willebrand disease, use of anticoagulants such as warfarin) or known clotting disorders (e.g., hypercoagulable states).
12. Inability to maintain INR ≤1.4 using short-acting and long-acting procoagulants (e.g., recombinant human coagulation factor VIIa, fresh frozen plasma, vitamin K, etc.).
13. Subjects necessitating long-term anticoagulation therapy are excluded from participation. Reversal of anticoagulation is permissible for medically stable patients who can feasibly tolerate the short-term risks associated with reversal. Patients must not require Coumadin (warfarin) or other anticoagulants during the initial 30-day period.
14. Prior to the onset of symptoms, anticoagulants such as dabigatran, apixaban, or rivaroxaban, as well as treatments like tirofiban, ticagrelor, cilostazol, or clopidogrel, were used.
15. Internal bleeding involving the retroperitoneal, gastrointestinal, or genitourinary system, or respiratory tract bleeding.
16. Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures, etc.) or site of recent surgical intervention.
17. Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
18. Allergy/sensitivity to TNK.
19. Prior enrollment in the study.
20. Engagement in a concurrent interventional clinical investigation or trial. Patients enrolled in observational, natural history, or epidemiological studies that do not involve any form of intervention remain eligible.
21. Not expected to survive until the day 180 visit due to co-morbidities, or having DNR/DNI status (Do-Not-Resuscitate and Do-Not-Intubate) prior to randomization.
22. The presence of any concurrent serious illness that could confound outcome assessments, including but not limited to hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, or hematologic disorders.
23. Patients with mechanical heart valves are excluded. The presence of bioprosthetic valve(s) is permissible.
24. Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis. Atrial fibrillation without mitral stenosis is permitted.
25. Any other condition that, in the investigator's judgment, would present a significant risk to the subject if the investigational therapy were to be initiated.
26. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
27. Patients deemed by the investigator to have unstable conditions that may benefit from other treatments.
28. Patients requesting conservative treatment or standard craniotomy microsurgery treatment.
29. The subject or their legal guardian/representative demonstrates an inability or lack of willingness to provide written informed consent.

Where this trial is running

Beijing, China

• Beijing Tiantan Hospital — Beijing, China, China (RECRUITING)

Study contacts

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

Conditions: Deep Intracerebral Hemorrhage, Tenecteplase, Neuronavigation-assisted Stereotactic, Deep intracerebral hemorrhage