Clinical trial NCT00650858: Clinical Trial on Treatment of Intraventricular Hemorrhage
Official title: Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (IVH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intraventricular Hemorrhage
Keywords: Intraventricular hemorrhage (IVH)
rt-PA
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
name: Genentech, Inc.
First posted: 2008-04-02
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 30-day Mortality
timeFrame: 30 days
measure: Incidence of Bacterial Ventriculitis, Meningitis
timeFrame: 30 days
measure: Rate of Symptomatic Bleeding Events
timeFrame: 30-days
Secondary outcomes:
measure: Average Daily Percentage Clot Size Resolution Over the First 3 Days
timeFrame: 3 days
measure: 90 Day Follow-Up Modified Rankin Scale (mRS) Score
timeFrame: 90 days
measure: 90 Day Follow-Up Glasgow Outcome Scale (GOS) Score
timeFrame: 90 days
measure: 180 Day Follow-Up Modified Rankin Scale (mRS) Score
timeFrame: 180 days
measure: 180 Day Follow-Up Glasgow Outcome Scale (GOS) Score
timeFrame: 180 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: CR Drew Medical Center
state: California
city: Palo Alto
country: United States
facility: Standford Medical Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Systems
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas HSC, San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia, Charlottesville
state: Virginia
city: Fairfax
country: United States
facility: INOVA Fairfax Medical Center
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
Study officials:
affiliation: Johns Hopkins University
name: Daniel F Hanley, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.