Intracerebral Hemorrhage LobarPhase 3NALICE-TNKNCT07471256
Neuronavigation-assisted Stereotactic Minimally Invasive Puncture With Tenecteplase for Acute Lobar Intracerebral Hemorrhage
A Phase 3 study testing Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase and Standard medical treatment in people with Intracerebral Hemorrhage Lobar, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
Introduction: Minimally invasive puncture surgery with thrombolysis is effective for hypertensive intracerebral hemorrhage, but its effect on neurological recovery remains uncertain. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Intracerebral Hemorrhage Lobar
- What is being tested?
- Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase and Standard medical treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 636 participants
- Where
- 1 siteChina
- Study dates
- 31 Mar 2026to 31 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth<5 mL as measured by ABC/2 method).
- Randomization should occur within 6 to 24 hours after the diagnostic CT.
- Systolic blood pressure (SBP) less than 180 mmHg maintained for a duration of six hours, documented proximate to the randomization time point.
- Historical modified Rankin (mRS) score of 0 or 1.
Who cannot join
- 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.
- Patients presenting with an unstable intracranial mass or progressive intracranial compartment syndrome.
- National Institutes of Health Stroke Scale (NIHSS) score ≤ 5.
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- Presence of puncture contraindications.
- Irreversible impairment of brainstem function, characterized by bilateral fixed and dilated pupils, extensor motor posturing, and a Glasgow Coma Scale (GCS) score of ≤ 4.
- 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 herniatio.
- CT evidence suggesting a high risk of rebleeding, such as spot sign.
- Platelet count <100,000/mL; INR >1.4.
- Any irreversible coagulation disorders (e.g., hemophilia, von Willebrand disease, use of anticoagulants such as warfarin) or known clotting disorders (e.g., hypercoagulable states).
- 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.).
- 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 8-week period.
- 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.
- Internal bleeding involving the retroperitoneal, gastrointestinal, or genitourinary system, or respiratory tract bleeding.
- 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.
- Positive urine or serum pregnancy test in pre-menopausal female subjects without a documented history of surgical sterilization.
- Allergy/sensitivity to TNK.
- Prior enrollment in the study.
- 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.
- 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.
- 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.
- Patients with mechanical heart valves are excluded. The presence of bioprosthetic valve (s) is permissible.
- 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.
- 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.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Patients deemed by the investigator to have unstable conditions that may benefit from other treatments.
- Patients requesting conservative treatment or standard craniotomy microsurgery treatment.
- The subject or their legal guardian/representative demonstrates an inability or lack of willingness to provide written informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Beijing Tiantan Hospital, Beijing, China 100000
Beijing
Jinyi Tang, +86 13219378078, strive0225@163.com
About this study
Official title: Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined With Tenecteplase for the Treatment of Acute Spontaneous Lobar Intracerebral Hemorrhage(NALICE-TNK)： a Randomized, Outcome-blinded, Multi-center Trial
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.
Read more
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.
Read the detailed description
The 2024 Brief Report on Stroke Prevention and Treatment in China indicates that the incidence rate of spontaneous intracerebral hemorrhage in China was 61/100,000 in 2021. Among these, acute spontaneous lobar intracerebral hemorrhage has become a major cause of stroke and related deaths, resulting in high disability and mortality rate. The surgical treatment of lobar hemorrhage has been a prominent research focus in neurosurgery. The STICH Ⅱ trial demonstrated that, for patients with spontaneous supratentorial lobar hemorrhage, early craniotomy for hematoma evacuation did not significantly improve functional prognosis compared to conservative medical treatment. Nevertheless, the ENRICH trial showed that, compared to standard medical treatment, early stereotactic minimally invasive puncture and drainage significantly improved the 90-day functional prognosis of patients with acute intracerebral hemorrhage, with this benefit also being robust in the lobar hemorrhage subgroup. The study further underscores that minimally invasive surgery is not universally applicable: patient selection requires systematic integration of multiple evidence-informed factors, including hematoma volume and morphology, deep versus lobar anatomical location, time from symptom onset to intervention, baseline neurological severity (e.g., NIHSS score), and major systemic comorbidities, into a comprehensive, individualized treatment decision.
In the 2022 guidelines for intracerebral hemorrhage, minimally invasive procedures (MIPS) are recommended as a Class 2a intervention due to their mortality-reducing benefit. MIPS under stereotactic or neuronavigation guidance represents a technically sound approach with relatively robust evidence and high clinical accessibility. It is highly standardized and has low dependence on medical resources, making it feasible for implementation in centers with basic neuroimaging and perioperative management capabilities.
Several multicenter randomized controlled trials, such as MISTIE II, MISTIE III, and ENRICH, have confirmed that minimally invasive techniques, including stereotactic minimally invasive puncture and drainage and neuroendoscopic hematoma evacuation, can significantly reduce the 90-day all-cause mortality rate in patients with spontaneous intracerebral hemorrhag. In these studies, the mortality rate in the minimally invasive treatment group was lower than that in the corresponding standard medical treatment control group. Despite baseline differences, pooled data show 90-day mortality was 18-26% with standard medical treatment and 9-19% with minimally invasive treatment. Although MIPS has been proven to reduce surgical complications compared to craniotomy, its efficacy in reducing long-term neurological dysfunction remains uncertai. In the STICH trial, the incidence of neurological dysfunction in the minimally invasive puncture group was 36.1%, higher than 26.5% in the conservative treatment group. Similarly, the MISTIE II trial, led by the Hanley team, observed a similar trend, with the 90-day composite endpoint of disability or death in the minimally invasive puncture group being 73.0%, slightly higher than 69.0% in the conservative treatment group. However, in the more rigorous MISTIE III trial, this endpoint difference between the two groups was no longer statistically significant (71.8% vs. 72.0%, P = 0.94). It is noteworthy that the subgroup analysis of the MISTIE III trial showed that patients who received minimally invasive surgery and had their postoperative residual hematoma volume reduced to <15 mL experienced significantly better 90-day functional outcome compared to those in the standard medical treatment group. This suggests that extensive and rapid hematoma evacuation can effectively improve patient prognosis. Therefore, future trials should prospectively assess whether combining early aggressive evacuation with minimally invasive surgery can outperform the current standard and further enhance functional outcomes.
Precise localization of the catheter tip at the center of the hematoma is essential for efficient hematoma evacuation, as it directly influences the gravity-dependent diffusion distribution of thrombolytic agents within the hematoma cavity, thereby determining the efficiency of clot dissolution. The liquefied hematoma components are also drained through the same catheter. The combination of neuronavigation and stereotactic techniques significantly improves the accuracy of target localization. Additionally, preoperative planning based on CT angiography helps avoid blood vessels, reducing the risk of brain tissue injury and secondary hemorrhage due to puncture.
Tenecteplase (TNK), a third-generation tissue plasminogen activator derived from alteplase (rt-PA), offers several significant pharmacological advantages. Firstly, TNK has a substantially longer plasma half-life than rt-PA, allowing for a single intravenous bolus administration instead of the continuous infusion required by rt-PA, simplifying the clinical medication regimen and enhancing operational feasibility. Secondly, TNK has greater resistance to plasminogen activator inhibitor-1 (PAI-1), helping maintain stable enzymatic activity and thereby enhancing thrombolytic efficacy, especially in treating hematoma formation secondary to acute intracerebral hemorrhage, with potential benefits. Furthermore, TNK has higher specificity for fibrin, selectively activating plasminogen within local thrombi while reducing systemic plasminogen activation, thereby effectively minimizing bleeding complications, including severe or diffuse bleeding events. These pharmacological properties have been validated in numerous large-scale clinical studies on myocardial infarction and acute ischemic stroke. Recent studies have also shown that TNK can accelerate the enzymatic degradation and clearance of blood clots, thus facilitating hematoma resolution. However, high-quality evidence supporting the effectiveness and safety of neuronavigation-assisted stereotactic minimally invasive puncture combined with TNK (NALICE-TNK) in improving functional prognosis in patients with acute spontaneous lobar hemorrhage is currently lacking.
The NALICE-TNK trial aims to determine whether neuronavigation-guided stereotactic minimally invasive puncture combined with tenecteplase improves functional outcomes in patients with acute spontaneous lobar intracerebral hemorrhage compared to standard drug therapy. This multicenter, randomized, outcome-blinded trial will evaluate the efficacy and safety of neuronavigation-assisted stereotactic minimally invasive puncture combined with thrombolysis using tenecteplase in reducing disability and mortality rates in patients with spontaneous lobar intracerebral hemorrhage. This article outlines the design and protocol of the trial.
- Conditions
- Intracerebral Hemorrhage Lobar
- Being tested
- Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase, Standard medical treatment
- Keywords
- Neuronavigation-assisted Stereotactic, Lobar intracerebral hemorrhage, Minimally invasive puncture, Tenecteplase (TNK), Multicenter randomized trial, Hematoma evacuation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with TenecteplaseProcedure or surgery
Neuronavigation-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 treatmentDrug
The 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
| Study group | Role | What they receive |
|---|---|---|
| Standard medical treatment group | Sham comparator | The standard medical treatment for this group of patients will be provided according to the optimal care standards outlined by the American Heart Association (AHA) for the management of intracerebral hemorrhage. Receives: Drug: Standard medical treatment |
| NALICE-TNK group | Experimental | This intervention involves neuronavigation-assisted stereotactic minimally invasive puncture for acute spontaneous lobar intracerebral hemorrhage (NALICE) combined with tenecteplase (TNK) . NALICE enhances catheter placement precision, reducing complications and improving hematoma evacuation and neurological outcomes. TNK, a third-generation thrombolytic, 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. Receives: Procedure: Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 180 ±14 days
All-cause death at 30 days post-randomization
All-cause death at 30 days post-randomization
Measured: 30-day post-randomization period
Secondary outcomes (16)
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.
Measured: 180 ± 14 days
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.
Measured: 180 ±14 days
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.
Measured: 180 ± 14 days
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.
Measured: 30 days post-randomization
Residual hematoma volume at 24 hours post the final administration.
The residual volume of the hematoma was calculated through CT examination 24 hours after the last administration of TNK (using the ABC/2 method).
Measured: 24 hours after the last administration of TNK
Dichotomized eGOS (extended Glasgow Outcome Scale) score at 180 days: 4-8 (good) vs. 1-3(poor)
Dichotomized eGOS (extended Glasgow Outcome Scale) score at 180 days: 4-8 (good) vs. 1-3 (poor). The eGOS is scored as: 1=Death, 2=Vegetative state, 3=Lower severe disability, 4=Upper severe disability, 5=Lower moderate disability, 6=Upper moderate disability, 7=Lower good recovery, 8=Upper good recovery.
Measured: 180 ± 14 days
Functional ambulation of patients with mRS scores of 0-3 (good functional outcome) at 90 days post-randomization.
Functional ambulation of patients with mRS scores of 0-3 (good functional outcome) at 90 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: 0-3=No symptoms to moderate disability requiring some assistance; 4-6=Moderately severe disability requiring complete assistance to death.
Measured: 90 ± 7 days
All-cause death at 180 days post-randomizationl
All-cause death at 180 days post-randomizationl.
Measured: 180 ± 14 days
Barthel Index (BI) assessment at 180 days post-randomization
Barthel Index (BI) assessment at 180 days post-randomization. The Barthel Index (BI) assesses ten functional tasks of daily living, and each task provides a measure for level of independence. Scores range from 0 and 100, with a higher score indicating greater independence.
Measured: 180 ±14 days
Extended Glasgow Outcome (eGOS) assessment at 180 days post-randomization
Extended Glasgow Outcome (eGOS) assessment at 180 days post-randomization. The extended Glasgow Outcome Scale (eGOS) is a global scale for functional outcome with eight categories: 1 - Death, 2 - Vegetative State, 3 - Lower Severe Disability, 4 - Upper Severe Disability, 5 - Lower Moderate Disability, 6 - Upper Moderate Disability, 7 - Lower Good Recovery, 8 - Upper Good Recovery.
Measured: 180 ± 14 days
The change of the National Institutes of Health Stroke Scale (NIHSS) at 5-7 days or discharge if earlier from baseline
The change of the National Institutes of Health Stroke Scale (NIHSS) at 5-7 days or discharge if earlier from baseline. Patients with a NIHSS score of less than 6 are considered to have a good recovery. The NIHSS is a 11-item scale that assesses language, motor function, sensory loss, consciousness, visual fields, extraocular movements, coordination, neglect, and speech. It is scored from 0 (no stroke symptoms) to 42 (severe stroke).
Measured: 5-7 days
Symptomatic rebleeding events within 7 days post-randomization
Symptomatic rebleeding events within 7 days post-randomization (defined as a persistent decrease in GCS motor score by more than 2 points, with a CT scan showing a new hematoma with a CT value greater than 72 HU and a volume exceeding 5 ml within the hematoma cavity and surrounding area compared to the prior scan).
Measured: Within 7 days
All-cause death at 7 days
All-cause death at 7 days
Measured: Within 7 days
30-day intracranial bacterial infection post-randomization
Intracranial bacterial infection within 30 days.
Measured: Within 30 days
Total Adverse Events (AEs) within 30 and 180 days
Total Adverse Events (AEs) across all coded organ systems that occurred within 30 and 180 days.
Measured: Within 30 and 180 days
Total Serious Adverse Events (SAEs) within 30 and 180 days
Total Serious Adverse Events (SAEs) within 30 and 180 days
Measured: Within 30 and 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2026
- Study start31 Mar 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intracerebral Hemorrhage LobarStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 636 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Yong Cao, Beijing Tiantan Hospital
- Investigators
- Yong Cao, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07471256
- Sponsor's protocol ID
- NALICE-TNK-ICH
- Acronym
- NALICE-TNK
- Status last verified
- Mar 2026
- First submitted
- 10 Mar 2026
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined With Tenecteplase for the Treatment of Acute Spontaneous Lobar Intracerebral Hemorrhage(NALICE-TNK)： a Randomized, Outcome-blinded, Multi-center Trial
- ClinicalTrials.gov ID
- NCT07471256
- Acronym / sponsor ID
- NALICE-TNK / NALICE-TNK-ICH
- Conditions
- Intracerebral Hemorrhage Lobar
- Keywords
- Neuronavigation-assisted Stereotactic, Lobar intracerebral hemorrhage, Minimally invasive puncture, Tenecteplase (TNK), Multicenter randomized trial, Hematoma evacuation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 636 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 31 Mar 2026 (estimated)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 13 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The 2024 Brief Report on Stroke Prevention and Treatment in China indicates that the incidence rate of spontaneous intracerebral hemorrhage in China was 61/100,000 in 2021. Among these, acute spontaneous lobar intracerebral hemorrhage has become a major cause of stroke and related deaths, resulting in high disability and mortality rate. The surgical treatment of lobar hemorrhage has been a prominent research focus in neurosurgery. The STICH Ⅱ trial demonstrated that, for patients with spontaneous supratentorial lobar hemorrhage, early craniotomy for hematoma evacuation did not significantly improve functional prognosis compared to conservative medical treatment. Nevertheless, the ENRICH trial showed that, compared to standard medical treatment, early stereotactic minimally invasive puncture and drainage significantly improved the 90-day functional prognosis of patients with acute intracerebral hemorrhage, with this benefit also being robust in the lobar hemorrhage subgroup. The study further underscores that minimally invasive surgery is not universally applicable: patient selection requires systematic integration of multiple evidence-informed factors, including hematoma volume and morphology, deep versus lobar anatomical location, time from symptom onset to intervention, baseline neurological severity (e.g., NIHSS score), and major systemic comorbidities, into a comprehensive, individualized treatment decision.
In the 2022 guidelines for intracerebral hemorrhage, minimally invasive procedures (MIPS) are recommended as a Class 2a intervention due to their mortality-reducing benefit. MIPS under stereotactic or neuronavigation guidance represents a technically sound approach with relatively robust evidence and high clinical accessibility. It is highly standardized and has low dependence on medical resources, making it feasible for implementation in centers with basic neuroimaging and perioperative management capabilities.
Several multicenter randomized controlled trials, such as MISTIE II, MISTIE III, and ENRICH, have confirmed that minimally invasive techniques, including stereotactic minimally invasive puncture and drainage and neuroendoscopic hematoma evacuation, can significantly reduce the 90-day all-cause mortality rate in patients with spontaneous intracerebral hemorrhag. In these studies, the mortality rate in the minimally invasive treatment group was lower than that in the corresponding standard medical treatment control group. Despite baseline differences, pooled data show 90-day mortality was 18-26% with standard medical treatment and 9-19% with minimally invasive treatment. Although MIPS has been proven to reduce surgical complications compared to craniotomy, its efficacy in reducing long-term neurological dysfunction remains uncertai. In the STICH trial, the incidence of neurological dysfunction in the minimally invasive puncture group was 36.1%, higher than 26.5% in the conservative treatment group. Similarly, the MISTIE II trial, led by the Hanley team, observed a similar trend, with the 90-day composite endpoint of disability or death in the minimally invasive puncture group being 73.0%, slightly higher than 69.0% in the conservative treatment group. However, in the more rigorous MISTIE III trial, this endpoint difference between the two groups was no longer statistically significant (71.8% vs. 72.0%, P = 0.94). It is noteworthy that the subgroup analysis of the MISTIE III trial showed that patients who received minimally invasive surgery and had their postoperative residual hematoma volume reduced to <15 mL experienced significantly better 90-day functional outcome compared to those in the standard medical treatment group. This suggests that extensive and rapid hematoma evacuation can effectively improve patient prognosis. Therefore, future trials should prospectively assess whether combining early aggressive evacuation with minimally invasive surgery can outperform the current standard and further enhance functional outcomes.
Precise localization of the catheter tip at the center of the hematoma is essential for efficient hematoma evacuation, as it directly influences the gravity-dependent diffusion distribution of thrombolytic agents within the hematoma cavity, thereby determining the efficiency of clot dissolution. The liquefied hematoma components are also drained through the same catheter. The combination of neuronavigation and stereotactic techniques significantly improves the accuracy of target localization. Additionally, preoperative planning based on CT angiography helps avoid blood vessels, reducing the risk of brain tissue injury and secondary hemorrhage due to puncture.
Tenecteplase (TNK), a third-generation tissue plasminogen activator derived from alteplase (rt-PA), offers several significant pharmacological advantages. Firstly, TNK has a substantially longer plasma half-life than rt-PA, allowing for a single intravenous bolus administration instead of the continuous infusion required by rt-PA, simplifying the clinical medication regimen and enhancing operational feasibility. Secondly, TNK has greater resistance to plasminogen activator inhibitor-1 (PAI-1), helping maintain stable enzymatic activity and thereby enhancing thrombolytic efficacy, especially in treating hematoma formation secondary to acute intracerebral hemorrhage, with potential benefits. Furthermore, TNK has higher specificity for fibrin, selectively activating plasminogen within local thrombi while reducing systemic plasminogen activation, thereby effectively minimizing bleeding complications, including severe or diffuse bleeding events. These pharmacological properties have been validated in numerous large-scale clinical studies on myocardial infarction and acute ischemic stroke. Recent studies have also shown that TNK can accelerate the enzymatic degradation and clearance of blood clots, thus facilitating hematoma resolution. However, high-quality evidence supporting the effectiveness and safety of neuronavigation-assisted stereotactic minimally invasive puncture combined with TNK (NALICE-TNK) in improving functional prognosis in patients with acute spontaneous lobar hemorrhage is currently lacking.
The NALICE-TNK trial aims to determine whether neuronavigation-guided stereotactic minimally invasive puncture combined with tenecteplase improves functional outcomes in patients with acute spontaneous lobar intracerebral hemorrhage compared to standard drug therapy. This multicenter, randomized, outcome-blinded trial will evaluate the efficacy and safety of neuronavigation-assisted stereotactic minimally invasive puncture combined with thrombolysis using tenecteplase in reducing disability and mortality rates in patients with spontaneous lobar intracerebral hemorrhage. This article outlines the design and protocol of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard medical treatment group | Sham comparator | Drug: Standard medical treatmentThe standard medical treatment for this group of patients will be provided according to the optimal care standards outlined by the American Heart Association (AHA) for the management of intracerebral hemorrhage. |
| NALICE-TNK group | Experimental | Procedure: Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with TenecteplaseThis intervention involves neuronavigation-assisted stereotactic minimally invasive puncture for acute spontaneous lobar intracerebral hemorrhage (NALICE) combined with tenecteplase (TNK) . NALICE enhances catheter placement precision, reducing complications and improving hematoma evacuation and neurological outcomes. TNK, a third-generation thrombolytic, 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Stability CT scan done at least 6 hours after diagnostic CT showing clot stability (growth<5 mL as measured by ABC/2 method).
Key exclusion criteria (30 listed)
- 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.
- Patients presenting with an unstable intracranial mass or progressive intracranial compartment syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with TenecteplaseNeuronavigation-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. | Procedure or surgery | NALICE-TNK group |
| Standard medical treatmentThe 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 | Drug | Standard medical treatment group |
Primary outcome
Proportion of participants with mRS 0-3 at 180 days
Time frame: 180 ±14 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
Time frame: 30-day post-randomization period
All-cause death at 30 days post-randomization
16 secondary outcomes
Functional independence of patients with adjudicated mRS of 0-2 at 180 days post-randomization.
Time frame: 180 ± 14 days
Excellent functional outcome of patients with adjudicated mRS of 0-1 at 180 days post-randomization.
Time frame: 180 ±14 days
Distribution of mRS scores (0-6) at 180 days post-randomization.
Time frame: 180 ± 14 days
Distribution of mRS scores (0-6) at 30 days post-randomization
Time frame: 30 days post-randomization
Residual hematoma volume at 24 hours post the final administration.
Time frame: 24 hours after the last administration of TNK
Dichotomized eGOS (extended Glasgow Outcome Scale) score at 180 days: 4-8 (good) vs. 1-3(poor)
Time frame: 180 ± 14 days
Functional ambulation of patients with mRS scores of 0-3 (good functional outcome) at 90 days post-randomization.
Time frame: 90 ± 7 days
All-cause death at 180 days post-randomizationl
Time frame: 180 ± 14 days
Barthel Index (BI) assessment at 180 days post-randomization
Time frame: 180 ±14 days
Extended Glasgow Outcome (eGOS) assessment at 180 days post-randomization
Time frame: 180 ± 14 days
The change of the National Institutes of Health Stroke Scale (NIHSS) at 5-7 days or discharge if earlier from baseline
Time frame: 5-7 days
Symptomatic rebleeding events within 7 days post-randomization
Time frame: Within 7 days
All-cause death at 7 days
Time frame: Within 7 days
30-day intracranial bacterial infection post-randomization
Time frame: Within 30 days
Total Adverse Events (AEs) within 30 and 180 days
Time frame: Within 30 and 180 days
Total Serious Adverse Events (SAEs) within 30 and 180 days
Time frame: Within 30 and 180 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yong Cao principal investigator
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase and Standard medical treatment in people with Intracerebral Hemorrhage Lobar, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yong Cao (+86 13601362306, caoyong@bjtth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of participants with mRS 0-3 at 180 days (time frame: 180 ±14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.