Longitudinal brain volume changes are associated with cognitive decline in patients with cerebral small vessel disease - a prospective cohort study: The run dmc study

Background: The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke (CLEAR) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose rt-PA plus eptifibatide in acute ischemic stroke (AIS). The objective of the CLEAR-FDR trial was to estimate the sICH rate in AIS patients treated with full dose rt-PA (0.9 mg/kg) plus eptifibatide (bolus 135 mcg/kg and 2 hour infusion at 0.75 mcg/kg/min) when rt-PA was initiated within three hours of symptom onset.

Methods: This was a single-arm, prospective, open-label, multi-site study. Patients aged 18–85 years treated with IV rt-PA within three hours of symptom onset were approached for participation and consent obtained in eligible patients. The primary outcome was the proportion of patients who experienced sICH as defined in the NINDS stroke trial within 36 hours. An independent clinical monitor and a neuroradiologist determined if a sICH had occurred. The stopping rule was three sICHs within the first 19 patients or four sICHs within 29 patients. With a sample size of 30, a two-sided 95% CI for a rate of 8% would be 0% to 18%.

Results: From October 2013 to December 2014, 27 AIS patients were enrolled. Median age was 73years (Range 33–85, IQR 65–80) and median NIHSS was 12 (Range 6–26, IQR 9–16). One sICH (4%, 95% CI 0.7%–18%) was observed.

Conclusion: These preliminary results support the safety of proceeding with a phase 3 trial evaluating reduced and/or full dose rt-PA combined with eptifibatide to improve outcomes after AIS. More detailed results will be presented at the conference.