Ultrasound-aided Therapy Better Than Stroke Drug Alone, Trial Finds
Using ultrasound in combination with the drug t-PA can improve
response to an ischemic stroke, according to a study involving 126
patients. This first-of-its-kind human trial compared the safety
and efficacy of ultrasound and t-PA versus use of t-PA alone. The
trial was funded in part by the National Institute of Neurological
Disorders and Stroke (NINDS), a component of the National Institutes
of Health (NIH). The finding appears in the November 18, 2004, issue
of the New England Journal of Medicine.
Since 1996, the clot-busting drug t-PA (tissue plasminogen activator)
has been the only FDA-approved therapy for acute ischemic stroke.
Previous studies have shown that t-PA, when administered within
3 hours of onset of ischemic stroke, can greatly improve a patient's
chance for a full recovery. t-PA cannot be used to treat the less
common hemorrhagic stroke.
Researchers wanted to test the effectiveness of using transcranial
Doppler ultrasound (TCD) in combination with t-PA, and to ensure
that ultrasound did not cause bleeding into the brain. Utrasound
is a safe, non-invasive, FDA-approved diagnostic test that uses
sound waves to measure blood flow velocity in large arteries. An
international team led by Andrei Alexandrov, M.D., associate professor
of neurology at the University of Texas-Houston School of Medicine,
examined 126 patients who suffered an ischemic stroke. All patients
received intravenous t-PA within 3 hours of stroke onset. The 63
patients in the control group received t-PA alone, while the other
63 patients received t-PA in combination with continuous TCD monitoring
that started shortly before the patients received the drug. A small
device attached to a head frame was used to deliver the ultrasound.
Results showed that 49 percent of patients who received continuous
ultrasound and t-PA showed dramatic clinical improvement and little
or no blockage within 2 hours after therapy began compared to 30
percent who received t-PA alone. Notably, 38 percent of the patients
who received continuous ultrasound and t-PA showed no blockage within
two hours, compared to 13 percent who received t-PA alone. In all,
73 percent of patients who received the combined therapy showed
complete or partial clearance of the clot, compared to 50 percent
in the control group. Bleeding into the brain was experienced by
4.8 percent of patients in both groups. This early improvement of
blood flow to the brain resulted in a trend that 13.5 percent more
patients who received continuous ultrasound and t-PA had recovered
completely by 3 months after stroke.
The team also found that patients who experienced complete clearance
of their clot within 2 hours following treatment had the greatest
likelihood of regaining body strength, speech, and other functions
affected by stroke. Researchers named the trial CLOTBUST (Combined
Lysis Of Thrombus in Brain ischemia Using transcranial ultrasound
and Systemic t-PA).
"In the past 30 years, scientists around the world have shown
that ultrasound is fast, gentle, and effective in helping t-PA to
break up clots. For the first time, we have demonstrated this benefit
in patients. This approach enhances flow to the brain and augments
clinical recovery within minutes of treatment initiation,"
said Dr. Alexandrov.
"Stroke can be devastating for patients and their caregivers,"
said Story C. Landis, Ph.D., NINDS director. "These initial
findings suggest that patients who receive the combined therapy
are able to leave the hospital with a greater chance for recovery
following an ischemic stroke. This is an excellent example of improving
on an existing therapy and providing better outcomes."
Ultrasound causes vibrations among the molecules on and within
clot structures, which in turn creates more binding sites for t-PA
interaction and subsequent clot breakdown. The researchers think
that this "jiggle" improves drug transport to and around
the clot and helps to open more blocked vessels faster than can
be expected with t-PA therapy alone.
The NINDS is funding additional research to standardize the combined
therapeutic delivery system and plans to study it in a larger group
of patients. Other NINDS-funded research is investigating the basic
biology of stroke, use of diagnostics, and treatment.
Stroke is the nation's third leading cause of death, behind heart
disease and cancer. Each year about 700,000 persons in the United
States have a stroke, with about 80 percent of them being ischemic
The NINDS is a component of the NIH within the Department of Health
and Human Services and is the nation's primary supporter of biomedical
research on the brain and nervous system.