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Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Primary Purpose

Subarachnoid Hemorrhage, Cerebral Vasospasm, Cerebral Aneurysm

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tissue Plasminogen Activator

About this trial

This is an interventional prevention trial for Subarachnoid Hemorrhage

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Rush University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Intraventricular tPA

Placebo

Arm Description

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 Dose 1 mL sterile saline

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Rate of intracranial infection

The presence of infection will require identification of an offending organism via CSF cultures.

Full Information

NCT ID

NCT01878136

First Posted

June 12, 2013

Last Updated

November 9, 2015

Sponsor

Rush University Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT01878136

Brief Title

Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Official Title

Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

Study Type

Interventional

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Time constraints

Study Start Date

March 2015 (undefined)

Primary Completion Date

September 2016 (Anticipated)

Study Completion Date

September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rush University Medical Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Subarachnoid Hemorrhage, Cerebral Vasospasm, Cerebral Aneurysm, Hydrocephalus

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intraventricular tPA

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo Dose 1 mL sterile saline

Intervention Type

Drug

Intervention Name(s)

Tissue Plasminogen Activator

Other Intervention Name(s)

Activase, Alteplase

Intervention Description

Dose: 1mg Q8 x 12 doses, or until clearance of blood from ventricles and cisterns Administration: intraventricular administration (through external ventricular drain)

Primary Outcome Measure Information:

Title

Composite Primary Outcome

Description

Time Frame

1-60 days after SAH

Secondary Outcome Measure Information:

Title

Rate of new intracranial hemorrhage

Description

New intracranial hemorrhage will be defined as any new parenchymal or ventricular hemorrhage occurring after the first dose of study drug/placebo.

Time Frame

1-14 days after SAH

Title

Rate of intracranial infection

Description

The presence of infection will require identification of an offending organism via CSF cultures.

Time Frame

1-14 after SAH

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Stephan Munich, MD

Organizational Affiliation

Rush University Medical Center, Department of Neurosurgery

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Roham Moftakhar, MD

Organizational Affiliation

Rush University Medical Center, Department of Neurosurgery

Official's Role

Study Director

Facility Information:

Facility Name

Rush University Medical Center

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

12. IPD Sharing Statement

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Effect of Intraventricular tPA Following Aneurysmal Subarachnoid Hemorrhage

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