A multicenter study led by Johns Hopkins doctors has
fine-tuned the dosage and timing for
administering clot-busting tissue plasminogen activator, or
tPA, to patients with strokes caused by
bleeding within the brain.
The treatment, as reported in May at the European
Stroke Conference in Nice, France, has
been shown to dramatically decrease death and disability in
patients with this typically lethal subset
"We've gone from what's usually an 80 percent death
rate in patients with this condition to an
80 percent survival rate," said study leader Daniel Hanley,
neurology at the Johns
Hopkins School of Medicine.
This condition, known as intracerebral hemorrhage or
ICH, causes blood to clot inside the
brain's interior cavities, building up pressure within the
brain. The higher pressure, along with
inflammation caused by chemicals in the trapped blood, can
irreversibly damage the brain, usually
leading to death or extreme disability. Until recently no
treatment existed for this subset of stroke.
The new research builds on a series of previous
studies designed to test the safety and
efficacy of clot-busting drugs in patients with ICH. This
treatment, developed by Hanley and his
colleagues, clears the trapped blood out of the brain by
bathing — and dissolving — the clot directly in
tPA. This drug normally isn't recommended for conditions
that involve bleeding, such as ICH, because
it can increase the risk of further hemorrhage. However,
since high-dose (80 to 100 milligrams) tPA is
effective at breaking up clots in other conditions, such as
heart attacks and other types of strokes,
Hanley and his colleagues wondered whether very low doses
of the drug might be a safe and effective
way to treat ICH.
The previous studies showed that giving tPA to ICH
patients hadn't significantly increased
bleeding or death, so in the latest study, Hanley and his
colleagues sought to determine the safest and
most effective treatment regimen using this drug.
At 20 hospitals located across the United States,
Canada, Great Britain and Germany, the
researchers recruited 52 patients recently diagnosed with
ICH. All the patients had received the
usual treatment for this condition, which consists of
placing a catheter inside the brain to release the
trapped blood. Using the same catheter as a conduit for
flooding tPA directly onto the clot, the
researchers put each patient on one of three treatment
regimens: 0.3 milligram of the drug every 12
hours, 1 milligram of the drug every 12 hours or 1
milligram of the drug every eight hours.
Tracking patients' progress with daily CT scans, the
researchers found that the clots dissolved
within three to four days on average, with patients on 1
milligram of tPA every eight hours dissolving
their clots about a day faster than those on the other
treatment regimens. This timing is about two to
three times faster than that of previous patients who
didn't receive tPA. Hanley said that additional
bleeding among all patients was minimal; those treated with
tPA weren't any more likely to have
additional hemorrhaging than those past patients who didn't
receive the drug.
One month after treatment, more than 80 percent of the
patients were alive, and 10 percent of
these had recovered enough to return to their jobs, the
"We think that this treatment is the most promising
story in brain hemorrhage in many years,"
Hanley said. "We've taken a condition that used to have an
extremely high rate of death and disability
and turned it around."
The researchers plan to launch a definitive trial to
test this treatment in 500 patients in the
Other Johns Hopkins researchers who participated in
this study are Wendy Ziai, Ricardo
Carhuapoma, Neal Naff, Becky Sullivan, Timothy Morgan, Eric
Melnychuk, Susan Rice, Amber Stahl,
Alison Kwon, Shannon LeDroux, Amanda Bistran, Sofia Syed
and Karen Lane.
This study was funded by the FDA Orphan Drug Program
and partially supported by a sponsored
research agreement and drug from Genentech.
For more about the trial, go to: