Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Phase 1

Withdrawn

• Conditions: Subarachnoid Hemorrhage; Cerebral Aneurysm; Cerebral Vasospasm; Hydrocephalus
• Interventions: Drug: Tissue Plasminogen Activator

• Registration Number: NCT01878136
• Lead Sponsor: Rush University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-06-12
• Study First Submitted QC: 2013-06-12
• Study First Posted: 2013-06-14
• Study Start: 2015-03
• Status Verified: 2015-11
• Last Update Submitted: 2015-11-09
• Last Update Posted: 2015-11-11
• Primary Completion: 2016-09
• Study Completion: 2016-09

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intraventricular tPA	Tissue Plasminogen Activator	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
Placebo	Tissue Plasminogen Activator	Placebo Dose 1 mL sterile saline

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Rate of intracranial infection	1-14 after SAH	The presence of infection will require identification of an offending organism via CSF cultures.
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.

Trial Locations

Locations (1)

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States