Inraventricular tPA for Intraventricular Hemorrhage

As neurocritical care intensivists eagerly await the results of CLEAR III trial, many have started to offer intraventricular tissue plasminogen activator (IV-tPA) on an off-label basis to patients who have intraventricular hemorrahges with high clot burden.

This blog reviews the procedure for IV-tPA as used in the CLEAR III trial.

Inclusion.  The study included the following patients:  age 18-80, symptom onset <24h prior to diagnostic CT scan, spontaneous ICH </= 30 cc and IVH obstructing the III and IV ventricles.  Patients with primary IVH were included in the study as well.  Both the ICH and IVH clot must demonstrate stability.  CT scan peformed 6 hours or more after catheter placement must show that the ICH size not differ by </=5cc compared to the previous CT.  Also, the width of the lateral ventricle that is affected most by the clot must not increase by 2mm.

Catheter tract bleeding must be </= 5cc on CT scan.  SBP should be <200 for the 6 hours prior to drug administration.

Exclusion.  The following patients were excluded from the trial:  patients wih suspected aneurysm (untreated), ruptured AVM or tumor, choroid plexus vascular malformatoin or Moyamoya disease, patients with clotting disorders, use of NOACs, platelet <100K, INR <1.4, pregnancy, infratentorial hemorrhage, thalamic bleeds, SAH, ongoing internal bleeding, bleeding at multiple vascular puncture and access sites.  Patients with treated aneurysm or AVM were included if treatment occurred at least 3 months before the current onset.

Intraventricular tPA procedure:

  1. Administer 1.0mg/mL of tPA via the EVD
  2. Flush with sterile saline (4mL) to clear tPA from the catheter
  3. Clamp EVD for 1 hour, and then open to drain clot and CSF until next injection
  4. Continue treatment every 8 hours for up to 12 doses of the drug


Dual Catheters.  For patients ith dual catheters, alternate the doses through each catheter every eight hours.  Once the III and IV ventricles are open, discontinue dosing via the catheter contralateral to the clot.  Continue  dosing through the ipsilesional ventricle until ~80% of the intraventricular clot has been removed, IVH-related shift has resolved, or a total of 12 doses have been administered.

Maintain ICP  <30 and CPP >70mm Hg.

Order CT scans on days 1-5 and then 1 and 3 days after the last dose of tPA.


  • diagnostic CT
  • diagnostic CTA or routine angiogram
  • EVD placement
  • stability CT
  • BP <200 over 6 hours
  • tox screen
  • go over inclusion and exclusion criteria
  • informed consent
  • start IV-tPA (1.0 mg q8h) up to 12 doses and open to drainx24h after last dose
  • CT scan on Days 1-5 and then 1 and 3 days after last dose
  • lab assessments daily from days 1-7


Primary Investigator:  Daniel F.Hanley, MD, NIH/NINDS, Johns Hopkins medical Institutions; CLEAR III:  Clot Lysis:  Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III


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