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.
In patients with spontaneous intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH) is often associated with catastrophic outcomes. Studies have reported that the mortality rate in ICH patients with IVH exceeds 50%, and fewer than 20% of survivors achieve good functional outcomes. Hematoma lysis therapy appears to influence both mortality and functional recovery. Previous systematic reviews and meta-analyses suggest that the removal of intraventricular hemorrhage, by alleviating acute obstructive hydrocephalus and reducing neurotoxicity, may improve survival rates and long-term functional outcomes. The CLEAR III trial, published in The Lancet, demonstrated that in patients with IVH and external ventricular drainage, the 180-day mortality rate was lower with intraventricular alteplase lavage compared to saline (0.9%), although functional outcomes did not improve. Alteplase, a second-generation fibrinolytic agent, facilitates the dissolution of hematomas following intraventricular hemorrhage. However, its low fibrin specificity, short half-life, and weak resistance to plasminogen activator inhibitor type 1 (PAI-1) often necessitate multiple thrombolytic administrations. This may explain the lack of improvement in neurological functional outcomes. In contrast, tenecteplase, a third-generation fibrinolytic agent, exhibits higher fibrin specificity and a longer half-life, which may enhance thrombolytic efficiency and hematoma clearance rates. These properties make tenecteplase a potentially safer and more effective option for hematoma dissolution in patients with intraventricular hemorrhage. Building on the findings of the CLEAR III trial and previous research, this study aims to replace alteplase with tenecteplase and conduct a prospective, single-center, "3+3" dose-escalation trial to evaluate the safety and optimal dosing of tenecteplase-assisted hematoma dissolution for intraventricular hemorrhage. The results will provide a foundation for future multicenter randomized controlled trials.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
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.
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.
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.
Beijing Tiantan Hospital
Beijing, Beijing Municipality, China
RECRUITINGDrug-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.
Time frame: 24, 48, 72, and 96 hours after the first dose tenecteplase administration.
Mortality rate
Death within 7 days of enrollment
Time frame: within 7 days of enrollment
Ventricular infection
fever and positive cerebrospinal fluid culture
Time frame: within 7 days of enrollment
Clot Removal
Change in blood volume measured between stability scan and 24 hours after the last dose.
Time frame: 24 hours after the last dose.
Number of doses administered at the endpoint of the treatment
Record the number of doses administered at the endpoint of the treatment.
Time frame: 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.
CT examinations were performed every 24 hours after tenecteplase administration to determine the resolution of 3rd and/or 4th ventricles obstruction.
Time frame: 24, 48, 72, and 96 hours after the first dose tenecteplase administration.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.