Thrombolytic therapy saves 1 in 10 patients with hemorrhagic stroke

By John Murphy, MDLinx
Published February 23, 2016

Key Takeaways

A thrombolytic agent given to patients with hemorrhagic stroke safely reduced mortality in 10% of treated patients when compared with control patients who received saline, according to researchers who presented their study results February 18, 2016 at the International Stroke Conference in Los Angeles, CA.

The drug, tissue plasminogen activator (tPA), has been used since the late 1990s to treat heart attacks and strokes caused by blood clots. In this six-year international multicenter trial (the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial, or CLEAR III), investigators combined tPA with extraventricular drainage to “flush” blood clots from the brains of patients with hemorrhagic stroke whose bleeding had stabilized.

“We found that using the clot-busting drug tPA meant that for every 10 patients treated, one life was saved,” said principal investigator Daniel Hanley Jr., MD, the Jeffrey and Harriet Legum Professor of Acute Care Neurological Medicine and Director of the Brain Injury Outcomes Program at the Johns Hopkins University School of Medicine, in Baltimore, MD. “Our results suggest that physicians should begin to think about routinely using it for stable hemorrhagic stroke patients.”

In addition, almost half of all treated patients went home by 6 months and could live independently.

Currently, no direct treatments for hemorrhagic stroke are approved or considered safe other than supportive care, or invasive surgery in severe cases. An estimated 40% to 80% of patients with hemorrhagic stroke die within 30 days, and only 20% of patients return home to live independently. Survivors often have paralysis, partial blindness, speech and cognitive disorders.

For this trial, the researchers recruited 500 patients from 73 research hospitals between 2009 and 2014. The trial included patients (ages 18 to 80) with small intracerebral hemorrhages accompanied by a large intraventricular hemorrhage. To qualify, subjects’ intracerebral blood clots and intracerebral bleeding had to be stable, as determined by repeated CT scans.

When a patient presented with stroke, a neurosurgeon or neurocritical care physician gave each patient treatment to lower intracranial pressure to stabilize the blood clot, and then inserted a catheter into the ventricle for the extraventricular drainage. Patients were randomized to receive an injection of either 1 mg of tPA or 1 ml of saline through the catheter for every 8 hours for up to 12 doses, or until the ventricles were cleared of blood. Each patient was evaluated at 1 month and 6 months.

At 6 months, the patients who received tPA had an overall mortality rate of 19% compared with 29% in patients who received placebo—a 10% decrease in mortality. Also, 49% of treated patients had adverse events compared with 62% in the saline control group, including fewer bacterial infections in the brain, bleeding, and pneumonia.

“Hemorrhage in the brain used to be an essentially untreatable condition, but we now have hope with a therapy that may be effective at saving lives,” said study coauthor and neurovascular surgeon Issam Awad, MD, the John Harper Seeley Professor of Surgery at the University of Chicago Medicine, in Chicago, IL.

However, decreased mortality was the secondary endpoint. The primary endpoint—improved functional outcomes—didn’t show a significant increase in treated patients. About half (48%) of patients given tPA were able to go home and live independently, which was about the same percentage (45%) as subjects given saline.

“We had estimated a 13% better disability score with the drug, and only got a 3% difference,” Dr. Hanley said. “This is going to make many physicians cautious, and rightly so, in terms of outcomes.”

But there was a silver lining to studying this treatment, he added. “We showed that using the extraventricular drain to flush blood from the brain greatly increased the number of patients able to go home and live independently. Outside our study, catheter drainage is used in only 8% of hemorrhagic stroke cases, and we showed this technique can really make a difference.”

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