By Matthew E. Fink, MD
Louis and Gertrude Feil Professor and Chair, Department of Neurology, Associate Dean for Clinical Affairs, NYP/Weill Cornell Medical College
Dr. Fink reports no financial relationships relevant to this field of study.
Alexandrov AV, Kohrmann M, Soinne L, et al. Safety and efficacy of sonothrombolysis for acute ischemic stroke: A multicenter, double-blind, phase 3, randomized controlled trial. Lancet Neurol 2019;18:338-347.
Currently, IV alteplase for thrombolysis is the only approved treatment for acute ischemic stroke worldwide. Despite the growing use of mechanical thrombectomy, most stroke centers around the world do not have this capability, and any treatment that might enhance the efficacy of IV thrombolysis would be a welcomed improvement. In a Phase II trial published in 2004 (Alexandrov AV, et al. N Engl J Med 2004;351:2170-2178), the use of 2 MHz pulsed Doppler with a portable transcranial Doppler device was shown to double the rate of recanalization of middle cerebral artery occlusions. Investigators then organized a Phase III randomized trial to evaluate the efficacy of this approach.
In this multicenter trial at 76 medical centers in 14 countries, 335 patients were randomly allocated to the intervention group and 341 patients to the control group. The investigators included patients who had an acute ischemic stroke with an NIH stroke scale score of ≥ 10 and who received IV thrombolysis within three hours of symptom onset in North America and 4.5 hours of symptom onset in other countries. The intervention group received active 2 MHz pulsed wave ultrasound for 120 minutes focused on the middle cerebral artery, and the control group received sham ultrasound. The ultrasound was delivered using a specially designed device that kept the ultrasound probe focused on middle cerebral artery without the need for an operator holding the probe. The primary outcome was improvement in the modified Rankin Scale score at 90 days.
The adjusted odds ratio for improvement in the modified Rankin Scale score at 90 days in the intervention group was 1.05 and in the control group 1.24, but these differences were not statistically significant. Adverse events were reported in approximately the same frequency in both groups. The investigators concluded that transcranial Doppler delivery of sonothrombolysis was feasible and safe, but showed no clinical benefit at 90 days. However, the investigators urged continuing investigation of this technology because many centers may not be able to offer thrombectomy. This treatment deserves further investigation and evaluation for potential benefit.
