Introduction: Minimally invasive puncture surgery with thrombolysis is effective for hypertensive intracerebral hemorrhage, but its effect on neurological recovery remains uncertain. The use of neuronavigation-assisted stereotactic technology can significantly improve the precision of catheter placement, while tenecteplase (TNK), a third-generation thrombolytic with high fibrin specificity and superior activity against platelet-rich clots. Nonetheless, the efficacy and safety of combining neuronavigation-assisted stereotactic minimally invasive puncture (NALCIE) with TNK for reducing disability and mortality in acute spontaneous lobar intracerebral hemorrhage have yet to be established.
Aim: To present the scientific rationale and study design of the neuronavigation-assisted stereotactic minimally invasive puncture combined with tenecteplase (NALICE-TNK) trial for the treatment of acute spontaneous lobar intracerebral hemorrhage.
Design: NALICE-TNK is a multicenter, randomized, open-label, assessor-blinded, clinical trial enrolling 636 patients with acute lobar intracerebral hemorrhage and hematoma volumes of 30-50 mL. The trial aims to assess the efficacy and safety of neuronavigation-assisted stereotactic minimally invasive puncture (MIPS) combined with tenecteplase (TNK), administered every 24 hours at a dose of 0.009 mg per mL of hematoma volume, versus standard medical care. All participants will undergo standardized 180-day follow-up.
Study outcomes: The primary efficacy endpoint is functional ambulation (a score of 0 to 3 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 180 days. The primary safety endpoint is all-cause mortality at 30 days.
Age ≥18 years and <80 years
Symptoms must have manifested within 24 hours prior to the diagnostic CT (dCT) scan. Patients with indeterminate symptom onset are excluded; for those who awoke with symptoms, the last known well time is used.
Acute spontaneous lobar intracerebral hemorrhage (ICH) occurring in the frontal lobe, parietal lobe, temporal lobe, or occipital lobe, with a volume between 30-50 mL, measured at the site using the ABC/2 method with radiographic imaging (CT, etc.).
Glasgow Coma Scale (GCS) score of 5-14.
Hemorrhage in the basal ganglia, thalamus, or subtentorial region, including posterior fossa and cerebellar hemorrhage.
Stability CT scan done at least 6 hours after diagnostic CT showing clot instability (growth ≥5 mL as measured by ABC/2 method).
Intraventricular hemorrhage necessitating intervention to address mass effect or midline shift attributable to trapped ventricle syndrome secondary to intraventricular hemorrhage (IVH)-related casting.
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.
Parallel
Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase
Procedure/SurgeryNeuronavigation-assisted stereotactic minimally invasive puncture will enhances catheter placement precision, reducing complications and improving hematoma evacuation and neurological outcomes. TNK, a third-generation thrombolytic will offers advantages over alteplase (rt-PA), including a longer half-life for rapid bolus administration and effective thrombolytic effects to dissolve clots and promote hematoma clearance.
Standard medical treatment
DrugThe standard medical treatment for this group of patients will be provided according to the optimal care standards defined by the American Heart Association (AHA) guidelines for intracerebral hemorrhage management
Proportion of participants with mRS 0-3 at 180 days
The primary outcome is the proportion of participants with a modified Rankin Scale (mRS) score of 0-3 (range, 0 to 6, with higher scores indicating more severe disability) at 180 days.
All-cause death at 30 days post-randomization
All-cause death at 30 days post-randomization
Functional independence of patients with adjudicated mRS of 0-2 at 180 days post-randomization.
Functional independence of patients with adjudicated mRS of 0-2 at 180 days post-randomization. The mRS is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. Dichotomized scores are: 0-2=No symptoms to slight disability; 3-6=Moderate disability requiring some assistance to death.
Excellent functional outcome of patients with adjudicated mRS of 0-1 at 180 days post-randomization.
Excellent functional outcome of patients with adjudicated mRS of 0-1 at 180 days post-randomization. The mRS is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death.
Distribution of mRS scores (0-6) at 180 days post-randomization.
Distribution of mRS scores (0-6) at 180 days post-randomization. The mRS is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death.
Distribution of mRS scores (0-6) at 30 days post-randomization
Distribution of mRS scores (0-6) at 30 days post-randomization. The mRS is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death.
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