CLOTBUST: Design of a Randomized Trial of Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke

Abstract

The aim of phase II CLOTBUST trial is to determine the rates of early complete recanalization and dramatic/early clinical recovery in TPA + TCD and TPA groups. The sample size is set at 126 patients since a medium effect size (.50) is anticipated for TPA + TCD group vs TPA alone to achieve combined primary end-point.

Ultrashort echo‐time MRI versus CT for skull aberration correction in MR‐guided transcranial focused ultrasound: In vitro comparison on human calvaria

“…Using MRI would avoid the inconvenience of obtaining a separate CT scan, streamline treatment planning by eliminating the need to import and register the CT images, and perhaps most importantly spare the patient from exposure to ionizing radiation. From a clinical perspective, skipping the CT acquisition step would decrease the overall procedure time and would thus be a great asset for ultrasonic treatment of intracerebral hemorrhage 18 and ischemic stroke, 19 either in conjunction with tissue plasminogen activator 20 or not, 21 for which "time is brain." 22,23 Furthermore, an in-situ acquisition might improve the accuracy of the aberration corrections, since it would eliminate the possibility of misaligning the imported CT.…”

Ultrasound-Assisted Thrombolysis for Stroke Therapy

“…Alexandrov et al 34 employed 2-MHz transcranial Doppler ultrasound to monitor flow in the middle cerebral artery in acute ischemic stroke patients, and observed an increase in the rate of sustained complete recanalization within two hours after the administration of rt-PA in those patients who were monitored with ultrasound. Unfortunately, another clinical trial utilizing transcranial 300-kHz ultrasound, the TRanscranial low-frequency Ultrasound-Mediated thrombolysis in Brain Ischemia (TRUMBI) trial, was ended early when 13 of 14 patients being treated with rt-PA and ultrasound had evident intracranial bleeding on MRI, compared to 5 of 12 treated with rt-PA alone, and 5 of them experienced symptomatic hemorrhage within three days of treatment 35.…”

General Medicine

“…Higher frequencies however, in the order of 1-2.2 MHz frequencies can also enhance TPA-induced thrombus dissolution and this frequency range is commonly used for diagnostic and monitoring procedures without problem. The CLOTBUST trial has recently published Phase I trial data showing that rtPA in ischaemic stroke when combined with 2 MHz TCD provides superior recanalization to rtPA alone (28,36,37). Full trial data are pending.…”