Clinical Trial on Treatment of Intraventricular Hemorrhage

Intraventricular Hemorrhage Clinical Trial

— CLEAR IVH  

Official title:

Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (IVH)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00650858
• Other study ID #: IVH05
• Secondary ID: ISRCTN47341677
• Status: Completed
• Phase: Phase 2
• First received: December 26, 2007
• Last updated: November 8, 2017
• Start date: February 2004
• Est. completion date: August 2008

Study information

• Verified date: November 2017
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intraventricular Hemorrhage

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Germany	University of Heidelberg	Heidelberg
United Kingdom	Newcastle General Hospital	Newcastle upon Tyne
United States	Albany Medical Center	Albany	New York
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Maryland Medical Systems	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia, Charlottesville	Charlottesville	Virginia
United States	University of Cincinnati	Cincinnati	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University	Detroit	Michigan
United States	INOVA Fairfax Medical Center	Fairfax	Virginia
United States	Hartford Hospital	Hartford	Connecticut
United States	Baylor College of Medicine	Houston	Texas
United States	CR Drew Medical Center	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mt. Sinai Medical Center	New York	New York
United States	Standford Medical Center	Palo Alto	California
United States	Temple University	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	St. Louis University	Saint Louis	Missouri
United States	University of Texas HSC, San Antonio	San Antonio	Texas
United States	Via Christi Regional Medical Center	Wichita	Kansas

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	FDA Office of Orphan Products Development, Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30-day Mortality	The number of subjects who died at or before the 30-day follow-up visit were determined as a measure of safety. If more than 50% of the subjects died at or before the 30-day follow-up visit, the study would have been stopped for full DSMB review.	30 days
Primary	Incidence of Bacterial Ventriculitis, Meningitis	The incidence of bacterial ventriculitis/meningitis was recorded to determine the safety of intraventricular administration of rt-PA. If 30% or more subjects experienced this event, the study would have been stopped for full DSMB review.	30 days
Primary	Rate of Symptomatic Bleeding Events	The rate of symptomatic brain bleeding events were recorded to determine the safety of intraventricular administrations of rt-PA. If 35% or more subjects experienced a symptomatic bleeding event prior to the 30-day follow-up visit, the study would have been stopped for a full DSMB review.	30-days
Secondary	Average Daily Percentage Clot Size Resolution Over the First 3 Days	Daily IVH clot volume resolution, as a percentage of stability CT IVH volume, averaged over the first 3 days, determined by CT scans	3 days
Secondary	90 Day Follow-Up Modified Rankin Scale (mRS) Score	90 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead.; (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)	90 days
Secondary	90 Day Follow-Up Glasgow Outcome Scale (GOS) Score	90 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery.; (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)	90 days
Secondary	180 Day Follow-Up Modified Rankin Scale (mRS) Score	180 day follow-up visit mRS score. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from 0 to 6: 0. No Symptoms, 1. No Significant Disability, 2. Slight Disability, 3. Moderate Disability, 4. Moderately Severe Disability, 5. Severe Disability and 6. Dead.; (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)	180 days
Secondary	180 Day Follow-Up Glasgow Outcome Scale (GOS) Score	180 day follow-up visit GOS score. The GOS is a scale used to determine the degree of recovery from patients with brain injury. There are five categories: 1. Dead, 2. Vegetative State, 3. Severe Disability, 4. Moderate Disability and 5. Good Recovery.; (Stage 1 patients only had 30 day scores, Stage 2 patients had 30 day, 90 day and 180 day scores collected)	180 days

External Links

•   CLEAR III Website