Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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This study will evaluate the hypothesis that the administration of intraventricular tPA reduces the rates of cerebral vasospasm and ventriculoperitoneal shunt-dependent hydrocephalus in patients with aneurysmal subarachnoid hemorrhage.

Official Title
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Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Conditions
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Subarachnoid Hemorrhage, Cerebral Vasospasm, Cerebral Aneurysm, Hydrocephalus

Intervention / Treatment
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* Drug: Tissue Plasminogen Activator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 years old. SAH due to aneurysm, as determined by CT angiogram or cerebral angiogram. Modified Fisher (mF) grade 3 or 4 SAH, defined as thick cisternal blood without (grade 3) or with (grade 4) intraventrciular blood. Exclusion of the aneurysm from the parent circulation by endovascular embolization (Raymond class I or II) within 48 hours of ictus. Ventriculostomy placement must occur prior to randomization. Informed consent obtained from the patient or patient's decision maker Exclusion Criteria: Determination by treating physician(s) that no ventriculostomy is needed. Presence of intrinsic clotting disorders (e.g. due to hepatic failure, nephrotic syndrome, etc). Subjects whose pharmacologic anticoagulation is reversed, as determined by PT/INR, PTT within our institution's normal range, will be permitted to participate in this study. Presence of significant anemia, defined as hemoglobin < 8 gm/dL. Patients who undergo endovascular techniques requiring post-operative dual anti-platelet therapy. Residual aneurysm sac filling (Raymond class III occlusion). Aneurysm or vessel perforation during the endovascular procedure. Presence of craniectomy. Significant neurologic disability prior to the onset of SAH. Determination that administration of tPA/placebo cannot be initiated within 72 hours of symptom onset. Presence of untreated intracranial aneurysms larger than 3mm on CT angiography or cerebral angiogram.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intraventricular tPA<br>Tissue Plasminogen Activator (tPA) Dose: 1 mg Q8 hr x 12 doses, or until blood is cleared from the ventricles and cisterns Adminstration: Intraventricular; via previously placed external ventricular drain | Drug: Tissue Plasminogen Activator<br>* Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain)<br>* Other names: Alteplase;|
| Placebo Comparator: Placebo<br>Placebo Dose 1 mL sterile saline | Drug: Tissue Plasminogen Activator<br>* Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain)<br>* Other names: Alteplase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Primary Outcome | The composite primary outcome will consist of the rates of ventriculoperitoneal shunt (VPS) placement, clinically significant vasospasm, and death. VPS placement serves as surrogate measure of hydrocephalus. These outcomes will be measured during the patient's hospitalization. | 1-60 days after SAH | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of new intracranial hemorrhage | New intracranial hemorrhage will be defined as any new parenchymal or ventricular hemorrhage occurring after the first dose of study drug/placebo. | 1-14 days after SAH | 
| Rate of intracranial infection | The presence of infection will require identification of an offending organism via CSF cultures. | 1-14 after SAH |