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

• All cause mortality [ Time Frame: 180 days ] [ Designated as safety issue: No ]
• Amount of residual blood [ Time Frame: 72 h ] [ Designated as safety issue: No ]
• Intensity of critical care management [ Time Frame: 30 days ] [ Designated as safety issue: No ]

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, Cathflo® Activase® 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).

• Drug: Cathflo Activase
  1.0 mg of Cathflo Activase will be administered via the intraventricular catheter every 8 hours for up to 12 doses
  Other Names:

  • Cathflo Activase
  • rt-PA
• Other: Normal saline
  1 ml of normal saline will be administered via the intraventricular catheter every 8 hours for up to 12 doses
  Other Name: normal saline

• Experimental: rt-PA
  administration of rt-PA via the intraventricular catheter
  Intervention: Drug: Cathflo Activase
• Placebo Comparator: Saline Placebo
  1 ml of normal saline administered via the intraventricular catheter
  Intervention: Other: Normal saline

Inclusion Criteria:

• Age 18-80
• Symptom onset less than 24 hrs prior to diagnostic CT scan
• Spontaneous ICH less than or equal to 30 cc or primary IVH
• IVH obstructing 3rd and/or 4th ventricles
• ICH clot stability at 6 hours or more post IVC placement
• IVH clot stability at 6 hours or more post IVC placement
• Catheter tract bleeding stability 6 hours or more post IVC placement
• EVD placed per standard medical care
• SBP less than 200 mmHg sustained for 6 hours prior to drug administration
• Able to randomize within 72 hours of diagnostic CT scan
• Historical Rankin of 0 or 1

Exclusion Criteria:

• Suspected or untreated ruptured cerebral aneurysm, AVM, or tumor
• Presence of a choroid plexus vascular malformation or Moyamoya
• Clotting disorders
• Platelet count less than 100,000, INR greater than 1.4
• Pregnancy
• Infratentorial hemorrhage
• SAH at clinical presentation
• ICH/IVH enlargement that cannot be stabilized in the treatment time window
• Ongoing internal bleeding
• Superficial or surface bleeding
• Prior enrollment in the study
• Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
• Planned or simultaneous participation (between screening and Day-30) in another interventional medical investigation or clinical trial.
• No subject or legal representative to give written informed consent

• National Institute of Neurological Disorders and Stroke (NINDS)
• Genentech