Ultrasound-enhanced thrombolysis for acute ischemic stroke: Phase I. Findings of the CLOTBUST trial

Background. Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA). Subjects and Methods. Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. Results. 55 patients (mean age 69 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with (3) 9 points) were treated at 125 +/- 36 minutes from symptom onset. TCD monitoring began at 117 +/- 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score: 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by;? 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (Phi r(2) = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%. Conclusions. Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.