rhTNK-tPA Thrombolytic Removal of Intraventricular Hemorrhage

NCT06814964 | Recruiting Phase 1 DMC

• 1 other identifier: rhTNK-tPA-IVH01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to determine the safety and optimal dose of clot lysis with rhTNK-tPA for intraventricular hemorrhage, using stereotactic guidance for extraventricular drain placement.

Conditions

Intraventricular Hemorrhage

Keywords

intraventricular hemorrhage; Stereotactic puncture therapy; rhTNK-tPA

Outcome Measures

Primary Outcomes (1)

• Drug-related new rebleeding events

  CT examinations were performed every 24 hours after tenecteplase 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 were defined as newly emitted blood.

  24, 48, 72, and 96 hours after the first dose tenecteplase administration.

Secondary Outcomes (5)

• Mortality rate

  within 7 days of enrollment

• Ventricular infection

  within 7 days of enrollment

• Clot Removal

  24 hours after the last dose.

• Number of doses administered at the endpoint of the treatment

  24, 48, 72, and 96 hours after the first dose tenecteplase administration.

• The rate of resolution of 3rd and/or 4th ventricles obstruction at the endpoint of treatment.

  24, 48, 72, and 96 hours after the first dose tenecteplase administration.

Study Arms (3)

Low dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

EXPERIMENTAL

Low dose tenecteplase (injection amount = volume of intraventricular hematoma × 0.009 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD. At least 4 ml of CSF is removed prior to injection of 1 ml of test article followed by a 3 ml flush of sterile saline into the ventricle. Injection is followed by closure of the catheter for 1 hour and then opening of the EVD for drainage of clot and CSF until the next injection every 12 hours. Treatment continues for up to 8 doses of test article unless, an treatment success endpoint of clot lysis is reached, or an adverse treatment endpoint occurs (e.g. new hemorrhage: compared with the previous time point CT, a CT value of \> 72Hu and a volume of \> 5ml). Treatment success endpoints are (i) both 3rd and 4th ventricles are open; (ii) IVH related mass effect \[dilated or shifted ventricle\] is resolved; or (iii) an estimated 80% resolution of the IVH clot has occurred from the time clot stability was established.

Drug: Low dose group

Medium dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

EXPERIMENTAL

Medium dose tenecteplase (injection amount = volume of intraventricular hematoma × 0.018 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD. At least 4 ml of CSF is removed prior to injection of 1 ml of test article followed by a 3 ml flush of sterile saline into the ventricle. Injection is followed by closure of the catheter for 1 hour and then opening of the EVD for drainage of clot and CSF until the next injection every 12 hours. Treatment continues for up to 8 doses of test article unless, an treatment success endpoint of clot lysis is reached, or an adverse treatment endpoint occurs (e.g. new hemorrhage: compared with the previous time point CT, a CT value of \> 72Hu and a volume of \> 5ml). Treatment success endpoints are (i) both 3rd and 4th ventricles are open; (ii) IVH related mass effect \[dilated or shifted ventricle\] is resolved; or (iii) an estimated 80% resolution of the IVH clot has occurred from the time clot stability was established.

Drug: Medium dose group

High dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

EXPERIMENTAL

High dose tenecteplase (injection amount = volume of intraventricular hematoma × 0.027 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD. At least 4 ml of CSF is removed prior to injection of 1 ml of test article followed by a 3 ml flush of sterile saline into the ventricle. Injection is followed by closure of the catheter for 1 hour and then opening of the EVD for drainage of clot and CSF until the next injection every 12 hours. Treatment continues for up to 8 doses of test article unless, an treatment success endpoint of clot lysis is reached, or an adverse treatment endpoint occurs (e.g. new hemorrhage: compared with the previous time point CT, a CT value of \> 72Hu and a volume of \> 5ml). Treatment success endpoints are (i) both 3rd and 4th ventricles are open; (ii) IVH related mass effect \[dilated or shifted ventricle\] is resolved; or (iii) an estimated 80% resolution of the IVH clot has occurred from the time clot stability was established.

Drug: High dose group

Interventions

Low dose group DRUG

The calculated injection amount of tenecteplase (tenecteplase injection amount = volume of intraventricular hematoma × 0.009 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD.

Low dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

Medium dose group DRUG

The calculated injection amount of tenecteplase (tenecteplase injection amount = volume of intraventricular hematoma × 0.018 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD.

Medium dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

High dose group DRUG

The calculated injection amount of tenecteplase (tenecteplase injection amount = volume of intraventricular hematoma × 0.027 mg/ml) was diluted to 1ml with sterile injection water, and administered via the EVD.

High dose rhTNK-tPA thrombolytic removal of intraventricular hemorrhage

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 18-80 years.
• Symptom onset within 24 hours prior to diagnostic CT scan. Patients with unknown onset time should be excluded. For patients with symptoms occurring during sleep, the time of symptom onset should be considered as the last time the patient was awake and asymptomatic.
• Spontaneous intracerebral hemorrhage (ICH) ≤ 30 ml，with intraventricular hemorrhage (IVH) \>20 ml obstructing the third and/or fourth ventricles.
• All patients must have an external ventricular drain (EVD) placed prior to enrollment: The EVD should be accurately positioned into the largest cerebrospinal fluid (CSF) pool or the least bloody site in the lateral ventricle using robotic stereotactic guidance.
• A stability CT scan performed ≥ 6 hours after EVD placement must confirm ICH clot stability: The ICH volume change should be ≤ 5 ml compared to the previous CT scan. If the stability CT scan shows a difference \> 5 ml, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a hematoma enlargement ≤ 5 ml and the ICH volume remains ≤ 35 ml, the patient is eligible.
• IVH clot stability: The width of the lateral ventricle most affected by the clot must not increase by \> 2 mm. If the stability CT scan shows a difference \> 2 mm, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a change ≤ 2 mm, the patient is eligible.
• Catheter tract bleeding on the stability CT scan must be ≤ 5 ml. If any CT slice shows catheter tract bleeding \> 5 ml, a repeat stability CT scan should be performed ≥ 12 hours later. Stability CT scans may be repeated every 12 hours within 72 hours of the diagnostic CT scan. If two consecutive CT scans show a change ≤ 5 ml and the total hematoma volume along the tract is ≤ 10 ml, the patient is eligible.
• On the stability CT scan, the third and/or fourth ventricles must be occluded with blood.
• Primary IVH (ICH = 0) is eligible.
• Sustained systolic blood pressure (SBP) \< 180 mmHg for at least 6 hours prior to enrollment. (Patients do not need to meet the SBP criteria throughout the screening period, but vital signs should remain stable during the enrollment window).
• No intraventricular thrombolytic treatment within 12 hours of symptom onset.
• Enrollment must be completed within 72 hours of the diagnostic CT scan. (The 72-hour limit may be extended with PI approval for reasons such as hematoma stability, INR stability, or other valid justifications).
• Pre-morbid modified Rankin Scale (mRS) score of 0 or 1.

You may not qualify if:

• Hemorrhage caused by aneurysms, arteriovenous malformations (AVM), tumors, or other identifiable causes. If the cause of ICH is unknown, CTA, DSA, or other definitive imaging must be performed during screening to rule out these causes. If imaging is negative, the patient is eligible.
• Presence of choroid plexus vascular malformation or Moyamoya disease.
• Hypercoagulable state or coagulopathy. Patients requiring long-term anticoagulation are excluded. Reversal of anticoagulation is permitted if long-term anticoagulation is not required.
• Use of anticoagulants (e.g., dabigatran, apixaban, rivaroxaban) or antiplatelet agents (e.g., tirofiban, ticagrelor, cilostazol, clopidogrel) within one week prior to symptom onset (aspirin is allowed).
• Platelet count \< 100,000 or INR \> 1.4.
• Pregnancy (positive serum or urine pregnancy test).
• Infratentorial hemorrhage.
• Thalamic hemorrhage with significant midbrain extension, third nerve palsy, or dilated and non-reactive pupils. Other supranuclear gaze abnormalities are not excluded. Posterior fossa or cerebellar hemorrhages are excluded.
• Subarachnoid hemorrhage (SAH) or any atypical hematoma location or appearance on diagnostic CT scan. Angiography (CTA, DSA, or MRA/MRI) must be performed to rule out other causes. If no source of bleeding is identified, the patient is eligible. Cortical SAH secondary to clot lysis is eligible.
• Unstable ICH/IVH with ongoing hematoma enlargement.
• Indications for craniotomy: ① Progressive decline in consciousness; ② Signs of brain herniation; ③ Hematoma located \< 1 cm from the cortical surface.
• Ongoing internal bleeding involving retroperitoneal, gastrointestinal, genitourinary, or respiratory tracts. Patients with prior bleeding that is clinically stable for ≥ 12 hours and without coagulopathy or bleeding disorders are eligible.
• Multifocal superficial bleeding at multiple vascular puncture or access sites (e.g., venipuncture, arterial puncture) or recent surgical sites.
• Any condition that, in the investigator's opinion, poses a significant risk to the patient or makes the patient unsuitable for the study.
• Planned or concurrent participation in another interventional clinical trial. Participation in observational, natural history, or epidemiological studies without intervention is allowed.

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100070, China

RECRUITING

MeSH Terms

Interventions

Population Groups

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Yong Cao

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong Cao

CONTACT

+86 13601362306; caoyong@bjtth.org

Shaozhi Zhao

CONTACT

+86 18801217693; sdsgzsz@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: February 7, 2025
• Study Start: March 1, 2025
• Primary Completion: May 1, 2025
• Study Completion: June 1, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-01

Locations

CN (1)