ISC 2009: "Counterintuitive" Treatment for IVH Improves Mortality, Functional Outcomes

Launch of a Large 500-Patient Trial Announced

Caroline Cassels

February 23, 2009

February 23, 2009 (San Diego, California) — Final data from the Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR-IVH) show that treating this usually lethal condition with low-dose tissue plasminogen activator (tPA) delivered directly to the clot by catheter not only dramatically improves survival but also improves patients' functional independence at 6 months.

In light of these promising findings, researchers announced that there will be a National Institutes of Health (NIH)–funded, multicenter 500-patient study launched sometime in 2009. The randomized trial will compare outcomes in IVH patients randomized to receive standard treatment with an external ventricular drain (EVD) or an EVD plus tPA.

Dr. Daniel F. Hanley

"We believe we can make a substantial difference in the lives of these patients and are very happy that our peers [at the NIH] have decided to invest in and test the hypothesis in a large 500-patient study," principal investigator Daniel F. Hanley, MD, from Johns Hopkins University, in Baltimore, Maryland, said at a news conference.

Presented here at the American Stroke Association International Stroke Conference 2009, the dose-response investigation of catheter-based delivery of tPA showed that at 6 months, 10% of the pilot study's 52 patients with a confirmed diagnosis of IVH with third or fourth ventricular obstruction had no lingering disability, with a modified Rankin Scale (mRS) score of 0 or 1.

An additional 40% had only mild to moderate disability and were independently caring for themselves at home at 180 days, although they required some assistance with everyday tasks such as lifting heavy objects.

Substantial Nihilism

Even those who were initially more severely disabled continued to improve months after treatment, with the majority scoring lower on disability assessments after 6 months compared with the same assessments taken at 30 days.

A subtype of intracerebral hemorrhage (ICH), IVH typically has a fatality rate of between 80% and 100%.

"With this treatment, it ends up having a 17% mortality rate, which is a substantial difference. Yet the treatment is not widely available, not well-known, and not well recognized," said Dr. Hanley.

Dr. Hanley said there has been concern among clinicians that using this "counterintuitive" treatment that employs low-dose tPA to treat brain hemorrhage would preserve life at the expense of function. However, he added, these latest findings show that this is not the case.

"I do think there is a substantial nihilism that comes from epidemiologic and observational studies from prior decades that has not been removed from the minds of physicians," he said.

Potential to Significantly Improve Outcomes

Developed by Dr. Hanley and colleagues, the treatment involves administering low doses of tPA over several days directly to the clot via a surgically implanted catheter once bleeding has stabilized.

Interestingly, said Dr. Hanley, none of the time-window rules, which apply in the administration of tPA for ischemic stroke, appear to be important in the treatment of IVH.

"What does appear to be important is getting the blood out [of the brain]," he said.

In order to be a candidate for treatment, patients had to have 2 consecutive computed tomography (CT) scans demonstrating that the bleeding had stopped and the clot had stabilized within 6 hours after catheter placement. According to Dr. Hanley, 90% to 95% of study participants met these criteria.

Via a surgically implanted catheter, tPA is delivered directly to the clot in a system that is closed for 1 hour to allow the drug to interact with the clot. The system is then opened up to facilitate drainage of the lysed clot materials.

Patients were monitored with daily CT scans, and investigators found that clots dissolved on average within 3 to 4 days.

Investigators found symptomatic bleeding occurred at a rate of about 4%. Other complications included a 2% rate of bacterial ventriculitis.

No Special Expertise Required

Because the procedure is relatively simple, uses currently available technology, and requires no special training, the CLEAR-IVH approach could easily be applied at most hospitals, said Dr. Hanley.

Asked by Medscape Neurology & Neurosurgery to comment on the study, Cheryl Bushnell, MD, an assistant professor of neurology at Wake Forest University Health Sciences, in Winston-Salem, North Carolina, said the findings offer hope for better patient outcomes.

"I think it is wonderful that we may have an additional treatment option that will allow us not just to drain but to remove the clot and potentially significantly improve patient outcomes. This is 1 of the pivotal questions the upcoming trial will answer," she said.

According to Dr. Hanley, ICH accounts for 10% of all strokes in the United States and affects approximately 100,000 Americans every year, most of who between the ages of 50 and 55 years.

The study was supported by Johns Hopkins University, the Food and Drug Administration Office of Orphan Products Development, and Genentech.

American Stroke Association International Stroke Conference 2009: Abstract 142. Presented February 19, 2009.

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