Key result
High-dose perflutren lipid microspheres with tPA and ultrasound causes ~27% higher sICH rate.
RCT (n=35)
2:1 ratio
Yes
Answers are grounded in this paper and cite their sources.
OBJECTIVE: Microspheres (microS) reach intracranial occlusions and transmit energy momentum from an ultrasound wave to residual flow to promote recanalization. We report a randomized multicenter phase II trial of microS dose escalation with systemic thrombolysis. METHODS: Stroke patients receiving 0.9mg/kg tissue plasminogen activator (tPA) with pretreatment proximal intracranial occlusions on transcranial Doppler (TCD) were randomized (2:1 ratio) to microS (MRX-801) infusion over 90 minutes (Cohort 1, 1.4ml; Cohort 2, 2.8ml) with continuous TCD insonation, whereas controls received tPA and brief TCD assessments. The primary endpoint was symptomatic intracerebral hemorrhage (sICH) within 36 hours after tPA. RESULTS: Among 35 patients (Cohort 1 = 12, Cohort 2 = 11, controls = 12) no sICH occurred in Cohort 1 and controls, whereas 3 (27%, 2 fatal) sICHs occurred in Cohort 2 (p = 0.028). Sustained complete recanalization/clinical recovery rates (end of TCD monitoring/3 month) were 67%/75% for Cohort 1, 46%/50% for Cohort 2, and 33%/36% for controls (p = 0.255/0.167). The median time to any recanalization tended to be shorter in Cohort 1 (30 min; interquartile range [IQR], 6) and Cohort 2 (30 min; IQR, 69) compared to controls (60 min; IQR, 5; p = 0.054). Although patients with sICH had similar screening and pretreatment systolic blood pressure (SBP) levels in comparison to the rest, higher SBP levels were documented in sICH+ patients at 30 minutes, 60 minutes, 90 minutes, and 24-36 hours following tPA bolus. INTERPRETATION: Perflutren lipid microS can be safely combined with systemic tPA and ultrasound at a dose of 1.4ml. Safety concerns in the second dose tier may necessitate extended enrollment and further experiments to determine the mechanisms by which microspheres interact with tissues. In both dose tiers, sonothrombolysis with microS and tPA shows a trend toward higher early recanalization and clinical recovery rates compared to standard intravenous tPA therapy. Ann Neurol 2009;66:28-38.
No takes yet. Share an insight, caveat, or question.
Molina et al. (2009) conducted an RCT in Stroke with proximal intracranial occlusions (n=35). Perflutren lipid microspheres (MRX-801) infusion with continuous transcranial Doppler insonation and systemic tPA vs. Systemic tPA (0.9 mg/kg) and brief transcranial Doppler assessments was evaluated on Symptomatic intracerebral hemorrhage (sICH) within 36 hours after tPA (p=0.028). Perflutren lipid microspheres plus tPA and ultrasound caused 0% sICH at 1.4ml vs 27% at 2.8ml and 0% in controls.
Synapse has enriched 10 related papers. Consider them for comparative context: