Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

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.

Study Overview

• Status: Withdrawn
• Conditions: Subarachnoid Hemorrhage; Cerebral Vasospasm; Cerebral Aneurysm; Hydrocephalus
• Intervention / Treatment: Drug: Tissue Plasminogen Activator

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intraventricular tPA; 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; Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain); Other Names: Alteplase; Activase
Placebo Comparator: Placebo; Placebo Dose 1 mL sterile saline	Drug: Tissue Plasminogen Activator; Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain); Other Names: Alteplase; Activase

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Investigators: Principal Investigator: Stephan Munich, MD, Rush University Medical Center, Department of Neurosurgery; Study Director: Roham Moftakhar, MD, Rush University Medical Center, Department of Neurosurgery

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): September 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: June 12, 2013
• First Submitted That Met QC Criteria: June 12, 2013
• First Posted (Estimate): June 14, 2013

Study Record Updates

• Last Update Posted (Estimate): November 11, 2015
• Last Update Submitted That Met QC Criteria: November 9, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Intracranial Hemorrhages; Hemorrhage; Aneurysm; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Intracranial Aneurysm; Hydrocephalus; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator; Plasminogen
• Other Study ID Numbers: 13011803