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Clinical Trial on Treatment of Intraventricular Hemorrhage (CLEAR IVH)

This study has been completed.
Sponsor:
Collaborators:
FDA Office of Orphan Products Development
Genentech
Information provided by (Responsible Party):
Daniel Hanley, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00650858
First received: December 26, 2007
Last updated: June 13, 2012
Last verified: June 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Intraventricular Hemorrhage
 Drug: tissue plasminogen activator, rt-PA (thrombolytic) (Cathflo)
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (IVH)

Resource links provided by NLM:

Drug Information available for: Alteplase
U.S. FDA Resources

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • 30-day Mortality [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.

  • Incidence of Bacterial Ventriculitis, Meningitis [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    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.

  • Rate of Symptomatic Bleeding Events [ Time Frame: 30-days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 1.) Rate of Clot Size Reduction at Days 4-5 Determined by CT Scans (Stages 1 and 2). [ Time Frame: 180 days ] [ Designated as safety issue: Yes ]
  • 2.) 90 and 180 -Day GOS, Rankin, Stroke Impact Scale (Stage 2 Only). [ Time Frame: 90 and 180 days ] [ Designated as safety issue: Yes ]

Enrollment: 52
Study Start Date: February 2004
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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.
 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.
Other Names:
  • rt-PA
  • Cathflo
  • Activase
Active Comparator: 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.
 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.
Other Names:
  • rt-PA
  • Cathflo
  • Activase
Experimental: 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.
 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.
Other Names:
  • rt-PA
  • Cathflo
  • Activase

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00650858

  Show 25 Study Locations
Sponsors and Collaborators
Johns Hopkins University
FDA Office of Orphan Products Development
Genentech
Investigators
Study Chair: Daniel F Hanley, MD Johns Hopkins University
  More Information

Additional Information:
CLEAR III Website  This link exits the ClinicalTrials.gov site

No publications provided by Johns Hopkins University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Daniel Hanley, Dr., Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00650858     History of Changes
Other Study ID Numbers: IVH05, ISRCTN47341677
Study First Received: December 26, 2007
Results First Received: March 12, 2009
Last Updated: June 13, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
Intraventricular hemorrhage (IVH)
rt-PA

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
 Fibrinolytic Agents
Plasminogen
Tissue Plasminogen Activator
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses
Hematologic Agents

ClinicalTrials.gov processed this record on May 19, 2013