Subarachnoid Hemorrhage, Cerebral Vasospasm, Cerebral Aneurysm, Hydrocephalus
Conditions
Brief summary
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.
Interventions
Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain)
Sponsors
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Primary Outcome | 1-60 days after SAH | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of new intracranial hemorrhage | 1-14 days after SAH | New intracranial hemorrhage will be defined as any new parenchymal or ventricular hemorrhage occurring after the first dose of study drug/placebo. |
| Rate of intracranial infection | 1-14 after SAH | The presence of infection will require identification of an offending organism via CSF cultures. |
Countries
United States
Outcome results
None listed