Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage - Full Text View

Purpose

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.

Condition	Intervention	Phase
Subarachnoid Hemorrhage Cerebral Vasospasm Cerebral Aneurysm Hydrocephalus	Drug: Tissue Plasminogen Activator	Phase 1 Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Resource links provided by NLM:

MedlinePlus related topics: Bleeding

Drug Information available for: Alteplase

Genetic and Rare Diseases Information Center resources: Hydrocephalus

U.S. FDA Resources

Further study details as provided by Stephan Munich, Rush University Medical Center:

Primary Outcome Measures:

Composite Primary Outcome [ Time Frame: 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:

Rate of new intracranial hemorrhage [ Time Frame: 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 [ Time Frame: 1-14 after SAH ]
The presence of infection will require identification of an offending organism via CSF cultures.


Enrollment:	0
Study Start Date:	March 2015
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	September 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: Activase Alteplase
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: Activase Alteplase

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01878136

Locations


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

Sponsors and Collaborators

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

More Information


Responsible Party:	Stephan Munich, Neurosurgery Resident, Rush University Medical Center
ClinicalTrials.gov Identifier:	NCT01878136 History of Changes
Other Study ID Numbers:	13011803
Study First Received:	June 12, 2013
Last Updated:	November 9, 2015

Additional relevant MeSH terms:


Aneurysm Intracranial Aneurysm Brain Diseases Hemorrhage Subarachnoid Hemorrhage Hydrocephalus Vasospasm, Intracranial Pathologic Processes Vascular Diseases Cardiovascular Diseases	Intracranial Hemorrhages Cerebrovascular Disorders Central Nervous System Diseases Nervous System Diseases Intracranial Arterial Diseases Plasminogen Tissue Plasminogen Activator Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017