• Neurology Clinical Trials
• Neuroimaging
• Ischemia
• Cerebrovascular Disease

Microspheres that are combined with systemic tPA and rational transcranial Doppler (TCD) show promise as a recanalization tool in patients with acute ischemic stroke if administered within 3 hours of stroke onset. Carlos A. Molina, MD, Vall d'Hebron Hospital, Barcelona, Spain, reported results from the Transcranial Ultrasound in Clinical SONolyis (TUCSON; NCT00504842) trial, identifying 1.4 mL of MRX-801 perflutren lipid microspheres (μS) as a safe dose that produces higher rates of recanalization (67% vs 33%; p=0.22) compared with controls.

Earlier studies have shown that TCD can safely enhance the thrombolytic activity of tPA and increase the rates of recanalization and stroke recovery [Alexandrov AV et al. New Engl J Med 2004]. When combined with microbubbles [Molina CA et al. Stroke 2006] or microspheres [Alexandrov AV et al. Stroke 2008], complete, sustained recanalization and clinical recovery rates are even higher. The ultrasonography transiently expands the microspheres, transmitting energy momentum to the surrounding fluids, thereby furthering the process of recanalization of blocked vessels.

The TUCSON study [Barreto AD et al. Int J Stroke 2009] enrolled 35 acute (<3 hours) ischemic stroke patients with proximal intracranial arterial occlusions. Cohort 1 (n=12) received IV-tPA + continuous 2-MHZ TCD + 1.4 mL μS, Cohort 2 (n=11) received IV-tPA + continuous 2-MHZ TCD + 2.8 mL μS, and controls (n=12) received IV-tPA + intermittent 2-MHZ TCD. Infusion was over a 90-minute period.

At baseline, the mean age in all groups was ∼65 years, mean NIHSS was ∼13, and mean blood pressure was ∼153/77 mm Hg. Approximately 23% of patients had grade 0–1 thrombolysis in brain ischemia (TIBI), and 77% presented with M1 middle cerebral artery occlusions.

No symptomatic intracerebral hemorrhages (sICHs) occurred in either Cohort 1 or controls; 3 (27%, with 2 fatal) sICHs occurred in Cohort 2. Patients with sICH had significantly (p<0.04) higher blood pressures during and after treatment.

Sustained complete, partial, and no recanalization was seen in 67%, 17%, and 17% of Cohort 1; 46%, 0%, and 55% of Cohort 2; and 33%, 25%, and 42% of control patients, respectively. Three-month mortality was 0% (Cohort 1), 30% (Cohort 2), and 0% (control). The median time to any recanalization tended to be shorter in Cohort 1 (30 min) and Cohort 2 (30 min) compared with controls (60 min; p=0.054). At 3 months, 75% of patients in Cohort 1, 50% in Cohort 2, and 36% in controls (p=0.167) achieved mRS scores of 0–1 (Table 1).

Dr. Molina listed several limitations of the study, including a relatively small sample size, the inability to extend enrollment, and the use of an operator-dependent technology, such as TCD. Although the results were encouraging, the study was terminated by the sponsor due to administrative reasons. The rate of sICH that was observed in Cohort 2 may have been related to excessive blood pressure. Alternatively, bleeding with the higher μS dose could have been related to greater mechanical stress to the endothelium and tissues. Further studies will be needed to assess this issue.

• © 2009 MD Conference Express