The study aims to investigate the effect of continuous tPA irrigation into the ventricles. Investigators believe it may be superior to the traditional every 8-hour bolus dosing and continuous isotonic solution irrigation alone. The protocol plans to analyze blood clearance and functional outcomes in the patients.

The study is a prospective randomized trial, evaluating the impact of continuous tissue plasminogen activator (TPA) infusion in the setting of intraventricular hemorrhage (IVH) with blinded endpoint adjudication. This trial will enroll adult patients admitted to the University of Kentucky with substantial IVH (primary IVH, intracranial hemorrhage [ICH] with IVH, and IVH secondary to subarachnoid hemorrhage [SAH]). Patients will undergo placement of an irrigating ventricular catheter as per standard of care. Ventricular catheter placement will occur in all patients at the discretion of the neurosurgical team. Procedural consent will proceed per institutional standard of care.

Following irrigating ventricular catheter placement, irrigation and drainage will occur as per standard of care. Current use of intrathecal TPA for large-volume IVH burden is left to the discretion of the attending neurosurgeon. No standard of care exists as to its current clinical use, and it is often used, although sporadically in this patient population. Following device placement and initiation of irrigation, informed consent will be obtained by the neurosurgical research team. Following consent of either the patient or LAR, patients will be randomized in a 1:1 permuted block fashion to receive either irrigation alone or irrigation with continuous TPA infusion.

Initiation of continuous TPA infusion should start within approximately 24 hours of drain placement. As per standard of care, daily head computed tomography (HCT) scans should be obtained. Irrigation rates of normal isotonic solution typically range from 30-90 cc/hour, depending on patient tolerance and intracranial pressure. Subjects randomized to the TPA arm will have the same range of irrigation rates, with the dose of TPA infused ranging from 4-6 mg/day.

CSF should be collected from patients enrolled in the study following enrollment but prior to randomization and TPA initiation and then daily for up to 10 days. Collected CSF will then be assessed using MSD proteomics and ELISA assays to assess the inflammatory response, intercellular signaling, and breakdown products of hematoma and TPA. Patient outcomes (ICU length of stay, overall LOS, disposition, NIHSS scores, and functional outcomes) will be collected and assessed as available in the clinical record.

Inclusion Criteria:

• Male or female, age 18 years and older
• Intraventricular hemorrhage requiring EVD placement for treatment as determined by the cerebrovascular neurosurgical faculty member caring for the patient as per standard of care
• Baseline mRS 0 or 1
• Consenting requirements met as outlined below

Exclusion Criteria:

• IVH of traumatic origin
• Inability to initiate treatment within 24 hours of presentation
• Incarcerated individuals, pregnant individuals, or other conditions as deemed by the investigator to potentially confound study data
• Presence of evidence of severe brainstem dysfunction on presentation (absence of brain stem reflexes, fixed/dilated pupils)