NCT06868511

Neuronavigation-assisted Stereotactic Puncture With Tenecteplase for Acute Intracerebral Hemorrhage

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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 732 (estimated)
• Sponsor: Beijing Tiantan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Background Minimally invasive puncture surgery followed by thrombolysis has been proven to be an effective approach for managing hypertensive intracerebral hemorrhage. Nevertheless, its impact on improving neurological outcomes remains controversial. The integration of neuronavigation-assisted stereotactic (NAS) technology will significantly help enhance the accuracy of catheter placement, while tenecteplase (TNK), a third-generation thrombolytic agent, with greater potency in lysing platelet-rich clots and heightened specificity for fibrin may improve thrombolysis efficiency. However, the efficacy and safety of combining NAS minimally invasive puncture combined with TNK in reducing disability and mortality rates among patients with acute spontaneous deep intracerebral hemorrhage remain unknown. Aim To evaluate the efficacy and safety of neuronavigation-assisted stereotactic MIPS combined with TNK thrombolysis （NAS-TNK）in reducing disability and mortality in patients with deep hypertensive intracerebral hemorrhage. Design NAS-TNK is a randomized, open-label, outcome-blinded multicenter trial, involving 732 participants with acute basal ganglia or thalamic hemorrhage with a hematoma volume ranging from 20-50 mL. This study will evaluate the efficacy and safety of NAS minimally invasive puncture combined with TNK, administered every 24 hours at a dose of 0.009 mg per milliliter of hematoma volume, compared to participants receiving standard medical care. All patients will be followed up for 180 days. Study outcomes The primary efficacy outcome is the proportion of subjects in the NAS-TNK group with a modified Rankin Scale (mRS) score between 0 and 3 at 180 days. The primary safety outcome is the all-cause death at 30-day. The NAS-TNK study will help improve our understanding of the benefits of NAS minimally invasive puncture combined with TNK in patients with acute spontaneous deep intracerebral hemorrhage. This ongoing research will provide Level I evidence to guide clinicians in managing acute intracerebral hemorrhage treatment options.

Detailed description

Every year, more than 5 million cases of brain hemorrhage are reported worldwide. Minimally invasive surgery (MIS) has been established as an effective approach for treating acute spontaneous intracerebral hemorrhage and has received endorsement from both international and national clinical guidelines. Randomized controlled trials, such as MISTIE II, MISTIE III, and ENRICH, have demonstrated that procedures involving minimally invasive puncture or endoscopic hematoma evacuation significantly lower mortality rates among patients suffering from intracerebral hemorrhage. Data from these studies indicate that the mortality rate in the minimally invasive treatment groups has decreased from 18% to 26% down to approximately 9% to 19%. Additionally, the 2022 guidelines published by the American Heart Association and the American Stroke Association recommend these minimally invasive techniques as the preferred surgical intervention for patients with hematoma volumes exceeding 20 to 30 milliliters. Minimally invasive puncture surgery (MIPS) combined with thrombolysis is particularly favored for its simplicity and broad applicability. This technique effectively aids in the evacuation of hematomas and alleviates pressure in cases of deep acute spontaneous intracerebral hemorrhages, all while minimizing the risk of iatrogenic injury and maximizing the protection of neural tissue. Although MIPS has shown promising outcomes in reducing procedure-related trauma, the long-term effectiveness of this method in preventing neurological deficits remains a subject of ongoing debate. Recent findings from the MISTIE III trial shed light on this issue. In this trial, the MISTIE group exhibited a mortality rate of 15% at 180 days, a significant reduction compared to the 23% observed in the standard care group (p=0.033). Furthermore, at 365 days, 45% of patients treated with MIPS achieved a modified Rankin Scale (mRS) score of 0 to 3, indicating favorable functional outcomes, compared to 41% in the standard medical care group, with no statistically significant difference observed between the two groups. Nonetheless, subgroup analyses from the MISTIE III trial indicated that patients who underwent surgical intervention and achieved a hematoma reduction to less than 15 mL experienced significantly improved functional outcomes compared to those who received conservative treatment. This suggests that, in clinically stable patients, more aggressive and rapid removal of intracerebral hematomas may effectively lower the risk of mortality and enhance functional outcomes. Therefore, conducting trials that focus on rapid and extensive removal of hematoma volumes combined with MIPS would be beneficial in achieving better functional results. The precise placement of the catheter tip within the hematoma is critical for the efficient and rapid evacuation of intracerebral hematoma. The thrombolytic agent delivered from the catheter tip relies on gravity to infiltrate and interact with the clot, thereby facilitating its dissolution. Simultaneously, the liquefied hematoma fluid is drained through the catheter tip. Neuronavigation-assisted stereotactic (NAS) technology can significantly enhance the accuracy of catheter tip placement, thereby reducing the risk of iatrogenic injuries and complications. Tenecteplase (TNK), a third-generation thrombolytic agent derived from alteplase (rt-PA), offers several advantages over its predecessor. Its extended half-life allows for rapid administration via bolus infusion, providing logistical benefits compared to rt-PA. Additionally, TNK demonstrates increased resistance to inactivation by plasminogen activator inhibitor-1, resulting in a greater potency for lysing platelet-rich clots. Its heightened specificity for fibrin may also contribute to a reduction in hemorrhagic complications, especially those associated with systemic bleeding. These benefits have been evidenced in studies focused on conditions such as myocardial infarction and acute ischemic stroke. TNK has also shown effective thrombolytic effects, aiding in the dissolution of clots and promoting hematoma clearance. However, the efficacy and safety of combining NAS-assisted minimally invasive puncture with TNK (NAS-TNK) to reduce disability and mortality rates in patients with acute spontaneous deep intracerebral hemorrhage remain uncertain. The NAS-TNK trial is designed to explore the impact of precise, rapid, and efficient clearance of hematoma volumes on the improvement of neurological function in patients. This multicenter, randomized, outcome-blinded study will evaluate the efficacy and safety of neuronavigation-assisted stereotactic MIPS combined with TNK thrombolysis in reducing disability and mortality rates in patients suffering from deep hypertensive intracerebral hemorrhage. This paper presents the design of the NAS-TNK trial and outlines its protocol in detail.

Conditions

• Deep Intracerebral Hemorrhage (ICH)

Interventions

Type	Name	Description
PROCEDURE	Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase	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.
DRUG	Standard medical treatment	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

Timeline

• Start date: 2025-04-25
• Primary completion: 2027-03-01
• Completion: 2027-09-01
• First posted: 2025-03-11
• Last updated: 2025-04-22

Locations

1 site across 1 country: China