Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III "CLEAR III"

Completed

Phase 3 Results N/A

Trial Description

The overall objective of this Phase III clinical trial is to obtain information from a population of 500 ICH subjects with intraventricular hemorrhage (IVH), representative of current clinical practice and national demographics of ICH regarding the benefit (or lack thereof) of IVH clot removal on subject function as measured by modified Rankin Scale (mRS). This application requests funding for five years to initiate a Phase III randomized clinical trial (RCT) testing the benefit of clot removal for intraventricular hemorrhage. The investigators propose to compare extraventricular drainage (EVD) use plus recombinant tissue plasminogen activator (rt-PA; Alteplase; Genentech, Inc., San Francisco, CA) with EVD+ placebo in the management and treatment of subjects with small intracerebral hemorrhage (ICH) and large intraventricular hemorrhage (IVH defined as ICH < 30 cc and obstruction of the 3rd or 4th ventricles by intraventricular blood clot).

Conditions

Interventions

  • Alteplase Drug
    Intervention Desc: IV
  • Saline Drug
    Other Names: Sodium Chloride
    Intervention Desc: Used as placebo for injection.
  • Normal Saline Drug
    Intervention Desc: 1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
    ARM 1: Kind: Experimental
    Label: 2
    Description: 1 ml of normal saline administered via the intraventricular catheter
    ARM 2: Kind: Experimental
    Label: Saline Placebo
    Description: 1 ml of normal saline administered via the intraventricular catheter
  • Cathflo Activase Drug
    Other Names: rt-PA
    Intervention Desc: 1.0 mg of Cathflo Activase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
    ARM 1: Kind: Experimental
    Label: rt-PA
    Description: administration of rt-PA via the intraventricular catheter

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patient will have diagnostic CT scan first. Patient will have IVC placed. Modified Rankin Scale performed. Patients will be randomized to one of two arms witnin 72 hours of CT: in experimental arm patient will receive 1.0 mg of Cathflo Activase administered via the intraventricular catheter every 8 hours for up to 9 doses or to the control arm where the patient will receive 1 ml of normal saline administered via the intraventricular catheter every 8 hours for up to 9 doses

Outcomes

Type Measure Time Frame Safety Issue
Primary Modified Rankin Scale.
Secondary All cause mortality; amount of residual blood; intensity of critical care management.
Primary Modified Rankin Scale 180 days No
Secondary All cause mortality 180 days No
Secondary Amount of residual blood 72 h No
Secondary Intensity of critical care management 30 days No
Primary Modified Rankin Scale (Dichotomized 0-3) 180 days No
Primary Modified Rankin Scale (Ordinal Scale) 180 days No
Primary Modified Rankin Scale (Dichotomized 0-4) 180 days No
Primary Random effects assessment of site effect (modified Rankin Scale 0-3) 180 days No
Primary Modified Rankin Scale (Longitudinal 0-3) 180 days No
Secondary Clot removal (Amount of residual blood) 72 h No
Secondary Safety/Mortality 30 days Yes
Secondary Adverse and Serious Adverse Events 180 days Yes
Secondary Predictors of Mortality using Cox Proportional Hazards Model 180 days Yes
Secondary Sub-Group Analyses 180 days No
Secondary Functional Status 180 days Yes
Secondary Quality of Life 180 days No

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