Minimally Invasive Surgery and RhTNK-tPA for Intracerebral Hemorrhage Evacuation

NCT06668441 | Completed Phase 1 DMC

• 1 other identifier: KY2024-210
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to determine the safety of using a combination of robot-assisted stereotactic puncture and clot lysis with rhTNK-tPA to remove intracerebral hemorrhage (ICH) and to provide dose evidence for a phase III clinical trial.

Conditions

Intracranial Hemorrhages; Cerebrovascular Disorders; Cerebral Hemorrhage; Hemorrhage

Keywords

Basal ganglia; Stereotactic puncture therapy; Cerebral Hemorrhage; rhTNK-tPA; Minimally Invasive Surgery

Outcome Measures

Primary Outcomes (1)

• Drug-related rebleeding events:

  CT examinations were performed at 24, 48, 72, and 96 hours after administration. Compared with the CT at the previous time point, a CT value of more than 72 HU and a volume of more than 5 ml found in and around the hematoma cavity were defined as newly emitted blood.

  Within 24 hours of the last dose

Study Arms (1)

Teneplase assisted dissolution of blood clot therapy

EXPERIMENTAL

After CT reexamination 6 hours after surgery, the calculated injection amount of teneplase (teneplase injection amount = volume of hematoma × concentration of ascending drug) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma in turn. 0.5ml normal saline was used to flush the pipeline, and the drainage tube was fixed and closed for 2 hours. After the medication has fully acted with the hematoma mass, the drainage tube is re-opened to allow gravity drainage. CT examination was performed at 24 hours, 48 hours, 72 hours and 96 hours. Continuation or termination of the trial based on CT results at 24 hours, 48 hours, 72 hours, 96 hours: Teneplase was discontinued when the surgical goal defined by the test was achieved (residual hematoma ≤10ml), or new blood events occurred (compared with the previous time point CT, a CT value of \> 72Hu and a volume of \> 6ml of the space found in an

Drug: Minimally invasive surgery plus low-dose rhTNK-tPA group; Drug: Minimally invasive surgery plus medium dose rhTNK-tPA group; Drug: Minimally invasive surgery plus high dose rhTNK-tPA group

Interventions

Minimally invasive surgery plus low-dose rhTNK-tPA group DRUG

The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.001mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.

Teneplase assisted dissolution of blood clot therapy

Minimally invasive surgery plus medium dose rhTNK-tPA group DRUG

The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.003mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.

Teneplase assisted dissolution of blood clot therapy

Minimally invasive surgery plus high dose rhTNK-tPA group DRUG

The calculated injection amount of teneplase (teneplase injection amount = volume of hematoma ×0.009mg) was diluted to 1ml with sterile injection water, and injected into the stereotaxically planned puncture path according to the location and size of the hematoma. The pipeline was rinsed with 0.5ml normal saline, and the drainage tube was fixed and closed for 2 hours, so that after the full effect of the drug on the hematoma mass was ensured. Re-open the drain to allow gravity drainage.

Teneplase assisted dissolution of blood clot therapy

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 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).
• Neuronavigation-assisted stereotactic MIPS should be performed 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 enrollment 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 Tongren Hospital, Capital Medical University,

Beijing, Beijing Municipality, 100730, China

Location

Related Publications (7)

• Zhou X, Chen J, Li Q, Ren G, Yao G, Liu M, Dong Q, Guo J, Li L, Guo J, Xie P. Minimally invasive surgery for spontaneous supratentorial intracerebral hemorrhage: a meta-analysis of randomized controlled trials. Stroke. 2012 Nov;43(11):2923-30. doi: 10.1161/STROKEAHA.112.667535. Epub 2012 Sep 18.

  PMID: 22989500 BACKGROUND

• Wang WZ, Jiang B, Liu HM, Li D, Lu CZ, Zhao YD, Sander JW. Minimally invasive craniopuncture therapy vs. conservative treatment for spontaneous intracerebral hemorrhage: results from a randomized clinical trial in China. Int J Stroke. 2009 Feb;4(1):11-6. doi: 10.1111/j.1747-4949.2009.00239.x.

  PMID: 19236490 BACKGROUND

• Scaggiante J, Zhang X, Mocco J, Kellner CP. Minimally Invasive Surgery for Intracerebral Hemorrhage. Stroke. 2018 Nov;49(11):2612-2620. doi: 10.1161/STROKEAHA.118.020688.

  PMID: 30355183 BACKGROUND

• Li M, Mu F, Su D, Han Q, Guo Z, Chen T. Different surgical interventions for patients with spontaneous supratentorial intracranial hemorrhage: A network meta-analysis. Clin Neurol Neurosurg. 2020 Jan;188:105617. doi: 10.1016/j.clineuro.2019.105617. Epub 2019 Nov 20.

  PMID: 31775069 BACKGROUND

• Hanley DF, Thompson RE, Rosenblum M, Yenokyan G, Lane K, McBee N, Mayo SW, Bistran-Hall AJ, Gandhi D, Mould WA, Ullman N, Ali H, Carhuapoma JR, Kase CS, Lees KR, Dawson J, Wilson A, Betz JF, Sugar EA, Hao Y, Avadhani R, Caron JL, Harrigan MR, Carlson AP, Bulters D, LeDoux D, Huang J, Cobb C, Gupta G, Kitagawa R, Chicoine MR, Patel H, Dodd R, Camarata PJ, Wolfe S, Stadnik A, Money PL, Mitchell P, Sarabia R, Harnof S, Barzo P, Unterberg A, Teitelbaum JS, Wang W, Anderson CS, Mendelow AD, Gregson B, Janis S, Vespa P, Ziai W, Zuccarello M, Awad IA; MISTIE III Investigators. Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial. Lancet. 2019 Mar 9;393(10175):1021-1032. doi: 10.1016/S0140-6736(19)30195-3. Epub 2019 Feb 7.

  PMID: 30739747 BACKGROUND

• Guo G, Pan C, Guo W, Bai S, Nie H, Feng Y, Li G, Deng H, Ma Y, Zhu S, Tang Z. Efficacy and safety of four interventions for spontaneous supratentorial intracerebral hemorrhage: a network meta-analysis. J Neurointerv Surg. 2020 Jun;12(6):598-604. doi: 10.1136/neurintsurg-2019-015362. Epub 2020 Jan 3.

  PMID: 31900351 BACKGROUND

• Wu Z, Wang M, Bai X, Tang J, Ni Y, Zhao S, Wang P, He Q, Huo R, Jiao Y, Wang D, Cao Y. Phase I dose-escalation study of tenecteplase, a third-generation fibrinolytic agent, combined with neuronavigation-assisted stereotactic minimally invasive puncture, in patients with acute spontaneous deep cerebral haemorrhage. Stroke Vasc Neurol. 2025 Sep 24:svn-2025-004389. doi: 10.1136/svn-2025-004389. Online ahead of print.

  PMID: 40992931 DERIVED

MeSH Terms

Conditions

Intracranial Hemorrhages; Cerebrovascular Disorders; Cerebral Hemorrhage; Hemorrhage

Interventions

Minimally Invasive Surgical Procedures

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Study Officials

• Yong Cao, MD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: deputy director

Study Record Dates

• First Submitted: October 30, 2024
• First Posted: October 31, 2024
• Study Start: November 4, 2024
• Primary Completion: January 27, 2025
• Study Completion: January 27, 2025
• Last Updated: March 7, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)