Clinical Trial on Treatment of Intraventricular Hemorrhage

NCT ID: NCT00650858

Last Updated: 2017-12-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-02-29

Study Completion Date

2008-08-31

Brief Summary

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The specific objective of this trial is to determine the lowest dose and dose frequency possible with the best pharmacokinetic and safety profile and it's ability to remove a blood clot from the ventricular system.

Detailed Description

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The purpose of this trial is to determine the efficacy and pharmacokinetics of intraventricular injections of multiple low doses of rt-PA. Sixteen subjects were already randomized to receive intraventricular injections of with 0.3 mg or 1.0 mg of rt-PA every 12 hours for up to 8 doses. Results of this stage (n=16) were then analyzed and the most effective dose of 1.0 mg was chosen to be used in the second stage (n=36) to determine the optimal frequency of dosing. We propose to test if this intervention facilitates more rapid clot resolution, complete recovery function and decreased mortality from this condition.

Conditions

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Intraventricular Hemorrhage

Keywords

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Intraventricular hemorrhage (IVH) rt-PA

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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0.3 mg rt-PA

In stage 1 of the protocol, dose finding, subjects were randomized to either this 0.3 mg dose arm or the 1.0 mg dose arm. Subjects in this arm (0.3 mg) received up to 8 doses of 0.3 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Group Type ACTIVE_COMPARATOR

tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

Intervention Type DRUG

0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.

1.0 mg rt-PA

In stage 1 of the protocol, dose finding, subjects were randomized to either this 1.0 mg dose arm or the 0.3 mg dose arm. Subjects in this arm (1.0 mg) received up to 8 doses of 1.0 mg rt-PA every 12 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Group Type ACTIVE_COMPARATOR

tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

Intervention Type DRUG

0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.

1.0 mg Rt-PA q8h

In stage 2 of the protocol, dose frequency, subjects received up to 8 doses of 1.0 mg of rt-PA (Cathflo) every 8 hours through the intraventricular catheter to treat intraventricular hemorrhage.

Group Type EXPERIMENTAL

tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

Intervention Type DRUG

0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.

Interventions

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tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)

0.3 mg and 1.0 mg of rt-PA (Cathflo) were administered every 12 hours (dose finding) and every 8 hours (dose frequency) via the intraventricular catheter to treat intraventricular hemorrhage.

Intervention Type DRUG

Other Intervention Names

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rt-PA Cathflo Activase

Eligibility Criteria

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Inclusion Criteria

1. Age 18-75
2. IVC placed as standard of care using less than or equal to 2 complete passes.
3. Spontaneous ICH less than or equal to 30 cc.
4. Able to receive first dose within 48 hours of CT scan diagnosing IVH (providing the time of symptom onset to diagnostic CT does not exceed 12 hours).
5. Clot size measured on CT scan done 6 hours after IVC placement must be equal to the presentation clot size plus or minus 5 cc (as determined by the AxBxC)/2 method).
6. ON stability CT scan either the 3rd or 4th ventricles are occluded with blood (no evidence of CSF flow on CT).
7. SBP \< 200 mmHg sustained for 6 hours.
8. Historical Rankin of 0 or 1.

Exclusion Criteria

1. Suspected or untreated aneurysm or AVM (unless ruled out by angiogram or MRA/MRI).
2. Clotting disorders.
3. Patients with platelet count \< 100,000, INR \> 1.7, PT \> 15s, or an elevated APTT.
4. Pregnancy (positive pregnancy test).
5. Infratentorial hemorrhage (i.e., parenchymal/posterior fossa hematoma; all cerebellar hematomas excluded).
6. SAH (An angiogram should be obtained when the diagnostic CT scan demonstrates subarachnoid hemorrhage or any hematoma location or appearance not strongly associated with hypertension. If the angiogram does not demonstrate a bleeding source that accounts for the hemorrhage, the patient is eligible for the study).
7. ICH enlargement during the 6-hour stabilization period (6 hour after IVC placement).
8. Internal bleeding, involving retroperitoneal sites, or the gastrointestinal, genitourinary, or respiratory tracts.
9. Superficial or surface bleeding, observed mainly at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or site of recent surgical intervention.
10. Known risk for embolization, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, and subacute bacterial endocarditis.
11. Prior enrollment in the study.
12. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated.
13. Participation in another simultaneous medical investigation or trial.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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FDA Office of Orphan Products Development

FED

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel F Hanley, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

CR Drew Medical Center

Los Angeles, California, United States

Site Status

Standford Medical Center

Palo Alto, California, United States

Site Status

Hartford Hospital

Hartford, Connecticut, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Via Christi Regional Medical Center

Wichita, Kansas, United States

Site Status

University of Maryland Medical Systems

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

St. Louis University

St Louis, Missouri, United States

Site Status

Albany Medical Center

Albany, New York, United States

Site Status

Mt. Sinai Medical Center

New York, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Temple University

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Texas HSC, San Antonio

San Antonio, Texas, United States

Site Status

University of Virginia, Charlottesville

Charlottesville, Virginia, United States

Site Status

INOVA Fairfax Medical Center

Fairfax, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Foothills Medical Centre

Calgary, Alberta, Canada

Site Status

University of Heidelberg

Heidelberg, , Germany

Site Status

Newcastle General Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

Countries

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United States Canada Germany United Kingdom

References

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Kornbluth J, Nekoovaght-Tak S, Ullman N, Carhuapoma JR, Hanley DF, Ziai W. Early Quantification of Hematoma Hounsfield Units on Noncontrast CT in Acute Intraventricular Hemorrhage Predicts Ventricular Clearance after Intraventricular Thrombolysis. AJNR Am J Neuroradiol. 2015 Sep;36(9):1609-15. doi: 10.3174/ajnr.A4393. Epub 2015 Jul 30.

Reference Type DERIVED
PMID: 26228884 (View on PubMed)

Ziai W, Moullaali T, Nekoovaght-Tak S, Ullman N, Brooks JS, Morgan TC, Hanley DF. No exacerbation of perihematomal edema with intraventricular tissue plasminogen activator in patients with spontaneous intraventricular hemorrhage. Neurocrit Care. 2013 Jun;18(3):354-61. doi: 10.1007/s12028-013-9826-1.

Reference Type DERIVED
PMID: 23463422 (View on PubMed)

Morgan TC, Dawson J, Spengler D, Lees KR, Aldrich C, Mishra NK, Lane K, Quinn TJ, Diener-West M, Weir CJ, Higgins P, Rafferty M, Kinsley K, Ziai W, Awad I, Walters MR, Hanley D; CLEAR and VISTA Investigators. The Modified Graeb Score: an enhanced tool for intraventricular hemorrhage measurement and prediction of functional outcome. Stroke. 2013 Mar;44(3):635-41. doi: 10.1161/STROKEAHA.112.670653. Epub 2013 Jan 31.

Reference Type DERIVED
PMID: 23370203 (View on PubMed)

Webb AJ, Ullman NL, Mann S, Muschelli J, Awad IA, Hanley DF. Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program. Stroke. 2012 Jun;43(6):1666-8. doi: 10.1161/STROKEAHA.112.650523. Epub 2012 Apr 3.

Reference Type DERIVED
PMID: 22474059 (View on PubMed)

Ziai WC, Muschelli J, Thompson CB, Keyl PM, Lane K, Shao S, Hanley DF. Factors affecting clot lysis rates in patients with spontaneous intraventricular hemorrhage. Stroke. 2012 May;43(5):1234-9. doi: 10.1161/STROKEAHA.111.641050. Epub 2012 Mar 1.

Reference Type DERIVED
PMID: 22382155 (View on PubMed)

Herrick DB, Ziai WC, Thompson CB, Lane K, McBee NA, Hanley DF. Systemic hematologic status following intraventricular recombinant tissue-type plasminogen activator for intraventricular hemorrhage: the CLEAR IVH Study Group. Stroke. 2011 Dec;42(12):3631-3. doi: 10.1161/STROKEAHA.111.625749. Epub 2011 Sep 22.

Reference Type DERIVED
PMID: 21940973 (View on PubMed)

Related Links

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http://www.cleariii.com

CLEAR III Website

Other Identifiers

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ISRCTN47341677

Identifier Type: REGISTRY

Identifier Source: secondary_id

IVH05

Identifier Type: -

Identifier Source: org_study_id