Robot-Assisted Hematoma Evacuation With Intrahematoma Tenecteplase for Post-Reperfusion PH2 Hemorrhagic Transformation (REPORT)

Symptomatic intracranial hemorrhage after reperfusion therapy is one of the most devastating complications of acute ischemic stroke and is associated with high mortality, especially in patients with PH2 hemorrhagic transformation and substantial mass effect. Current management is largely supportive and includes discontinuation of antithrombotic agents, correction of coagulation abnormalities, blood pressure control, and intracranial pressure management. However, medical treatment does not remove the hematoma or reverse the local toxic and space-occupying effects of blood products.

Open craniotomy may be lifesaving in selected patients, but it may also cause additional injury to already ischemic and vulnerable brain tissue. Robot-assisted stereotactic minimally invasive puncture and aspiration may provide a less disruptive method to evacuate hematoma, reduce mass effect, and preserve surrounding tissue. A prior phase I neuronavigation-assisted minimally invasive puncture study in spontaneous deep intracerebral hemorrhage identified 0.009 mg/mL of hematoma-volume-adjusted tenecteplase as the highest tested dose with acceptable safety and the greatest mean hematoma clearance. Because the present trial targets a different and higher-risk population, namely post-reperfusion therapy PH2 hemorrhagic transformation, the study remains phase I in intent but uses a fixed dose rather than a dose-escalation design.

This is a prospective, open-label, single-arm phase I trial enrolling 20 participants with symptomatic supratentorial PH2 hemorrhagic transformation after reperfusion therapy (intravenous thrombolysis, with or without bridging mechanical thrombectomy). Eligible hematomas may be deep or lobar and must be associated with clinically relevant neurological worsening and hematoma-related mass effect. Before puncture, all participants must undergo protocol-based correction of coagulation abnormalities and at least one stability CT scan confirming no ongoing rapid expansion. Robot-assisted stereotactic aspiration and catheter placement will then be performed. A repeat CT approximately 2 hours later must confirm no procedure-related rebleeding before intrahematoma tenecteplase is started.

Tenecteplase will be administered once daily through the indwelling catheter at a fixed dose of 0.009 mg/mL of residual hematoma volume, for up to 3 doses. Each dose will be diluted to 1 mL with sterile water for injection, followed by a 3 ml normal saline flush. The catheter will remain clamped for 2 hours and then reopened for drainage. Treatment will stop when any termination criterion is met, including symptomatic rebleeding, radiographic hematoma enlargement, residual hematoma of 10 mL or less, or completion of 3 doses.

The primary objective is safety, particularly symptomatic rebleeding within 72 hours after the procedure or first tenecteplase dose, defined as clinically relevant hematoma expansion at the original cavity or catheter tract accompanied by neurological deterioration. The main efficacy and feasibility objectives are to determine whether the procedure achieves protocol-defined hematoma reduction-residual hematoma volume<15 mL or <33% of baseline volume by end-of-treatment CT-and accurate catheter placement within 3 mm of the planned target on immediate postoperative imaging. Secondary outcomes include residual hematoma volume at Day 7 or end of treatment, the proportion of participants achieving residual hematoma ≤10 mL, any radiographic rebleeding through Day 7, and procedure-related serious adverse events（SAE） through Day 7.