Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
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Description Module
Ignite Creation Date:
2026-03-26 @ 3:17 PM
Ignite Modification Date:
2026-03-26 @ 3:17 PM
NCT ID:
NCT07471256
Brief Summary:
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:
NCT07471256
Study Brief:
Protocol Section:
NCT07471256