IRB Number:

09-002525

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

This study is a multicenter, international, double-blind, randomized study comparing the use of extraventricular drains (EVD) combined with rt-PA to EVD combined with placebo for the treatment of intraventricular hemorrhagic stroke. The purpose of this study is to examine the long-term effects of resolving blood clots on the functional outcomes of intraventricular hemorrhage patients. We will do this by evaluating if patients treated with rt-PA have a better functional outcome compared to patients treated with placebo.

Who is Eligible to Participate in the Study?

Inclusion Criteria:
1. Age 18-80
2. Symptom onset less than 24 hrs prior to diagnostic CT scan
3. All patients randomized will have had an EVD placed on an as a "standard of care" decision by the treating physicians
4. Systolic Blood Pressure < 200 mmHg sustained for the 6 hours before drug administration
5. Therapy will begin no sooner than 12 hours after symptom onset
6. Able to receive first dose within 72 hour of CT scan

Exclusion Criteria:
1. Suspected or untreated ruptured cerebral aneurysm, ruptured intracranial AVM, or tumor. Treatment of an existing aneurysm or AVM must have occurred at least 3 months before the current onset
2. Presence of a choroid plexus vascular malformation
3. Clotting disorders
4. Pregnancy
5. Infratentorial hemorrhage
6. Hemorrhage enlargement as determined by CT that cannot be stabilized within the treatment time window
7. Internal bleeding
8. Significant or serious superficial or surface bleeding, observed mainly at vascular puncture or access sites
9. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
10. Participation in another interventional medical investigation or interventional trial. Patients involved in observational, natural history, and/or epidemiological studies not involving an intervention are eligible
11. No subject or legal representative to give written informed consent

Minimum Age:

18

Maximum Age:

80

What is Involved With this Study?

If you agree to be in the study, you will be asked to participate in the following:

You will be put in one of 2 groups by chance (as in the flip of a coin). Patients randomly assigned to the intraventricular catheter(IVC) + rt-PA group will receive rt-PA through an IVC up to 12 times. Patients randomly assigned to the IVC + placebo group will receive normal saline through the IVC up to 12 times.

Your initial evaluation will include a medical history, physical examination, blood tests to see how your blood clots, urine for drug testing, tests of your neurological condition, and CT scans. If you are a woman of childbearing potential you will have a blood pregnancy test as part of your routine clinical care.

In order to be considered for participation in this study, your doctor must have decided it was necessary to surgically place an IVC inside your brain's ventricle. After IVC placement, you will have a CT scan about 6 hours later as part of your routine clinical care to make sure the IVC was placed correctly and to make sure there is no new bleeding in your brain. We will then inject about a teaspoon of rt-PA or placebo into the ventricles through the IVC every 8 hours up to a maximum of 12 times.

The drug/device used in this study is considered investigational, which means it has either not been approved by the Food and Drug Administration (FDA) for routine clinical use or for the use described in this study. However the FDA has allowed the use of this drug/device in this research study.

After each injection, the IVC will be closed for up to 1 hour, as tolerated, in order to allow the rt-PA or placebo to mix with the blood clot. We will stop the injections when the IVC is no longer needed or when enough blood has drained from the ventricles. Normal care includes the use of intravenous antibiotics or an IVC embedded eith antibiotics to reduce the risk of brain infection. A head CT scan will be done about every 24 hours to watch for any changes in the blood clot in the ventricles and for additional bleeding. A CT scan is a test that produces an image of your body using a small amount of radiation. The image shows the body tissues and structure in three dimensions (?3-D?). An additional CT scan will be done if your condition changes (either worsens or improves).

You will need to return to Mayo Clinic at 1, 6, and 12 months from the time of your initial hospitalization and enrollment in the study for a follow-up visit. At the 1-month and 12-month visits a follow-up head CT scan will be done to see if there have been any changes in your brain. We will also do neurological examinations to see how you are doing. These visits will take about 2 hours and will be video-recorded. This tape will be sent to an expert doctor in the United Kingdom for review. At 3 and 9 months we will call you on the telephone to see how you are doing. These phone calls will take about 30 minutes.

You will have approximately 2 tablespoons of blood drawn each morning during your stay in the ICU for up to 7 days as part of standard of care and on the day you are transferred out of the ICU.

Costs of Study:
You will not need to pay for tests and procedures which are done just for this research study. These tests and procedures are:

• The drug rt-PA or placebo


• The CT scans done on days 1-5 and 7


• The CT scans done for your follow-up visits at one month and 12 months


• Lab tests done as part of the protocol on days 1-7 and the day you are transferred out of the ICU. Specifically, CBC, PT/PTT, INR, Plasminogen, Fibrinogen, d-dimer, CSF culture, protein and glucose.

However, you and/or your health plan will need to pay for all other tests and procedures that you would normally have as part of your regular medical care. These tests and procedures are:

• All costs associated with the drain placement


• Any radiology tests not outlined above


• Any lab work not outlined above


• Any tests or procedures done prior to enrolling in the study


• All other routine care assessments

How long will the Study run?

One year

Who can I Contact for Additional Information on this Trial?

Alexa Richie, MPH, CCRP
904-953-7839
Richie.alexa@mayo.edu

What is/are the Locations of this Clinical Trial?

• Jacksonville, FL

Last updated: 07/06/2009