NCT06814964

rhTNK-tPA Thrombolytic Removal of Intraventricular Hemorrhage

A Phase I Pilot Clinical Trial of Dose Escalation With Stereotactic-Guided Intraventricular Thrombolysis Using Tenecteplase (rhTNK-tPA) for Intraventricular Hemorrhage.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Beijing Tiantan Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Intraventricular Hemorrhage

Interventions

Type	Name	Description
DRUG	Low dose group	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.
DRUG	Medium dose group	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.
DRUG	High dose group	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.

Timeline

• Start date: 2025-03-01
• Primary completion: 2025-05-01
• Completion: 2025-06-01
• First posted: 2025-02-07
• Last updated: 2025-02-27

Locations

1 site across 1 country: China