Intraventricular Brain Hemorrhage, Tissue Plasminogen Activator
Conditions
Brief summary
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.
Detailed description
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.
Interventions
Tissue Plasminogen Activator (tPA) is infused through the ClearRRAflow catheter into the ventricular system to promote clearance of intraventricular hemorrhage.
PROCEDUREIsotonic solution
Isotonic solution irrigation delivered through the CleaRRAflow catheter into the ventricular system to promote intraventricular hemorrhage clearance.
Sponsors
David Dornbos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion on the Speed of Intraventricular Hemorrhage (IVH) Clearance | Enrollment through 90 days | Assess through measurement of blood volume seen on imaging in the form of daily Head CT or Head MRI |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion on Ventricular Catheter Liberalization | Enrollment through 90 days | Record duration of time catheter is in place. Timepoints will be recorded from the medical record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion on the Inflammatory Proteomic Profile in Cerebrospinal Fluid (CSF) in Patients with Irrigating Ventricular Catheters | Baseline through 10 days | Using Meso scale discovery (MSD) platform with inflammatory marker panels, the proteomic profile of CSF will be evaluated. |
| Assess the Presence of Tissue Plasminogen Activator (TPA) within the Cerebrospinal Fluid (CSF) Following Administration | Baseline through 10 days | ELISA assay will be utilized to determine if TPA is present in CSF samples. |
| Assess the Breakdown of Tissue Plasminogen Activator (TPA) within the Cerebrospinal Fluid (CSF) Following Administration | Baseline through 10 days | ELISA assay will be utilized to determine the concentration of TPA present in CSF samples. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Shunt Dependency | Baseline through 90 days | Absence or Placement of shunt will be recorded from the clinical/medical record. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Functional Outcomes | Baseline through 90 days | Modified Rankin Score at Baseline, Discharge, and 90 day time points. |
| Assess the impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Mortality | Baseline through 90 days | Medical records will be reviewed and mortality will be documented at discharge and 90 days. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Ventilator Days | Baseline through 90 days | Medical records will be reviewed and number of days on ventilator will be documented. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on ICU Length of Stay | Baseline through 90 days | Medical records will be reviewed and number of days in the ICU will be documented. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Hospital Length of Stay | Baseline through 90 days | Medical records will be reviewed and number of days in the hospital will be documented. |
| Assess the Impact of Continuous Tissue Plasminogen Activator (TPA) Infusion in Patients with an Irrigating Ventricular Catheter on Hospitalization Costs | Baseline through 90 days | Hospitalization costs will be assessed by combining above outcome measures (ICU length of stay, time on ventilator, overall length of stay) |
Countries
United States
Contacts
CONTACTJennifer R Isaacs, MS, MS
Outcome results
None listed