Opeolu Adeoye1, Heidi Sucharew2, Jane Khoury2, Achala Vagal2, Pamela A Schmit2, Irene Ewing2, Steven R Levine2, Stacie Demel2, Bryan Eckerle2, Brian Katz2, Dawn Kleindorfer2, Brian Stettler2, Daniel Woo2, Pooja Khatri2, Joseph P Broderick2, Arthur M Pancioli2. 1. From the University of Cincinnati Neuroscience Institute, OH (O.A., P.A.S., I.E., S.D., B.E., B.K., D.K., B.S., D.W., P.K., J.P.B., A.M.P.); Departments of Emergency Medicine (P.A.S., I.E., B.S., A.M.P.), Neurosurgery (O.A.), Radiology (A.V.), and Neurology (S.D., B.E., B.K., D.K., D.W., P.K., J.P.B.), University of Cincinnati, OH; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, OH (H.S., J.K.); and Departments of Neurology and Emergency Medicine, The State University of New York (SUNY) Downstate Stroke Center and Medical Center, and King County Hospital Center, Brooklyn, NY (S.R.L.). Opeolu.Adeoye@uc.edu. 2. From the University of Cincinnati Neuroscience Institute, OH (O.A., P.A.S., I.E., S.D., B.E., B.K., D.K., B.S., D.W., P.K., J.P.B., A.M.P.); Departments of Emergency Medicine (P.A.S., I.E., B.S., A.M.P.), Neurosurgery (O.A.), Radiology (A.V.), and Neurology (S.D., B.E., B.K., D.K., D.W., P.K., J.P.B.), University of Cincinnati, OH; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, OH (H.S., J.K.); and Departments of Neurology and Emergency Medicine, The State University of New York (SUNY) Downstate Stroke Center and Medical Center, and King County Hospital Center, Brooklyn, NY (S.R.L.).
Abstract
BACKGROUND AND PURPOSE: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AIS patients treated with the combination of full-dose r-tPA plus eptifibatide. METHODS: CLEAR-FDR was a single-arm, prospective, open-label, multisite study. Patients aged 18 to 85 years treated with 0.9 mg/kg IV r-tPA within 3 hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 μg/kg bolus and 2-hour infusion at 0.75 μg/kg per minute) was administered. The primary end point was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if an sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was 3 sICHs within the first 19 patients or 4 sICHs within 29 patients. RESULTS: From October 2013 to December 2014, 27 patients with AIS were enrolled. Median age was 73 years (range, 34-85; interquartile range, 65-80) and median National Institute of Health stroke scale score was 12 (range, 6-26; interquartile range, 9-16). One sICH (3.7%; 95% confidence interval, 0.7%-18%) was observed. CONCLUSIONS: These results demonstrate comparable safety of full-dose r-tPA plus eptifibatide with historical rates of sICH with r-tPA alone and support proceeding with a phase 3 trial evaluating full-dose r-tPA combined with eptifibatide to improve outcomes after AIS.
BACKGROUND AND PURPOSE: The Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator (r-tPA; CLEAR) in Acute Ischemic Stroke (AIS) and CLEAR-Enhanced Regimen (CLEAR-ER) trials demonstrated safety of reduced dose r-tPA plus the glycoprotein 2b/3a inhibitor, eptifibatide, in AIS compared with r-tPA alone. The objective of the CLEAR-Full Dose Regimen (CLEAR-FDR) trial was to estimate the rate of symptomatic intracerebral hemorrhage (sICH) in AISpatients treated with the combination of full-dose r-tPA plus eptifibatide. METHODS: CLEAR-FDR was a single-arm, prospective, open-label, multisite study. Patients aged 18 to 85 years treated with 0.9 mg/kg IV r-tPA within 3 hours of symptom onset were enrolled. After obtaining consent, eptifibatide (135 μg/kg bolus and 2-hour infusion at 0.75 μg/kg per minute) was administered. The primary end point was the proportion of patients who experienced sICH within 36 hours. An independent clinical monitor adjudicated if an sICH had occurred and an independent neuroradiologist reviewed all images. The stopping rule was 3 sICHs within the first 19 patients or 4 sICHs within 29 patients. RESULTS: From October 2013 to December 2014, 27 patients with AIS were enrolled. Median age was 73 years (range, 34-85; interquartile range, 65-80) and median National Institute of Health stroke scale score was 12 (range, 6-26; interquartile range, 9-16). One sICH (3.7%; 95% confidence interval, 0.7%-18%) was observed. CONCLUSIONS: These results demonstrate comparable safety of full-dose r-tPA plus eptifibatide with historical rates of sICH with r-tPA alone and support proceeding with a phase 3 trial evaluating full-dose r-tPA combined with eptifibatide to improve outcomes after AIS.
Authors: Arthur M Pancioli; Opeolu Adeoye; Pamela A Schmit; Jane Khoury; Steven R Levine; Thomas A Tomsick; Heidi Sucharew; Claudette E Brooks; Todd J Crocco; Laurie Gutmann; Thomas M Hemmen; Scott E Kasner; Dawn Kleindorfer; William A Knight; Sharyl Martini; James S McKinney; William J Meurer; Brett C Meyer; Alexander Schneider; Phillip A Scott; Sidney Starkman; Steven Warach; Joseph P Broderick Journal: Stroke Date: 2013-07-25 Impact factor: 7.914
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