Neuronavigation-assisted Stereotactic Puncture With Tenecteplase for Acute Intracerebral Hemorrhage

NCT06868511 | Recruiting Phase 3 DMC

• 1 other identifier: NAS-TNK-ICH
• Study Type: interventional
• Target: 732
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Deep Intracerebral Hemorrhage (ICH)

Keywords

Tenecteplase; Neuronavigation-assisted Stereotactic; Deep intracerebral hemorrhage

Outcome Measures

Primary Outcomes (1)

• Modified Rankin Scale (mRS) score of 0-3 at 180 days.

  The primary efficacy outcome is the proportion of patients achieving a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 180 days.

  180 ±14 days

Secondary Outcomes (14)

• Dichotomized eGOS (extended Glasgow Outcome Scale) score at 180 days: 4-8 (good) vs. 1-3(poor)

  180 ± 14 days

• All-cause death at 180 days

  180 ± 14 days

• Dichotomized, modified Rankin Scale (mRS) Score 0-3 vs. 4-6 at 90 days.

  90 ± 7 days

• Dichotomized graded modified Rankin Scale (mRS) score at 180 days : 0-2 vs. 3-6.

  180 ± 14 days

• Ordinal graded modified Rankin Scale (mRS) score (0-6) at 180 days.

  180 ± 14 days

Study Arms (2)

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.

Drug: Standard medical treatment

NAS-TNK group

EXPERIMENTAL

This intervention involves neuronavigation-assisted stereotactic (NAS) minimally invasive puncture combined with tenecteplase (TNK). NAS minimally invasive puncture 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.

Procedure: Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase

Interventions

Neuronavigation-assisted Stereotactic Minimally Invasive Puncture Combined with Tenecteplase PROCEDURE

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.

NAS-TNK group

Standard medical treatment DRUG

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

Standard medical treatment group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years and \<80 years.
• 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.
• 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.).
• 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 Rankin score of 0 or 1.

You may not qualify if:

• Lobar or subtentorial hemorrhage, including posterior fossa hemorrhage 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.
• 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 herniation; 3) hematoma located within 1 cm of the cortical surface.
• 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 30-day 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.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, China, 100000, China

RECRUITING

MeSH Terms

Interventions

Tenecteplase

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Yong Cao

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong Cao

CONTACT

+86 13601362306; caoyong@bjtth.org

Zhiyou Wu

CONTACT

15880085161; 786392247@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 4, 2025
• First Posted: March 11, 2025
• Study Start: April 25, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 22, 2025

Record last verified: 2025-03

Locations

CN (1)