title: Combined Approach to Lysis Utilizing Eptifibatide and Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke-Full Dose Regimen Stroke Trial.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Opeolu
authors.initials: O
authors.lastname: Adeoye
authors.affiliation: 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.).
authors.forename: Heidi
authors.initials: H
authors.lastname: Sucharew
authors.affiliation: 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.).
authors.forename: Jane
authors.initials: J
authors.lastname: Khoury
authors.affiliation: 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.).
authors.forename: Achala
authors.initials: A
authors.lastname: Vagal
authors.affiliation: 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.).
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Schmit
authors.affiliation: 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.).
authors.forename: Irene
authors.initials: I
authors.lastname: Ewing
authors.affiliation: 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.).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.affiliation: 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.).
authors.forename: Stacie
authors.initials: S
authors.lastname: Demel
authors.affiliation: 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.).
authors.forename: Bryan
authors.initials: B
authors.lastname: Eckerle
authors.affiliation: 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.).
authors.forename: Brian
authors.initials: B
authors.lastname: Katz
authors.affiliation: 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.).
authors.forename: Dawn
authors.initials: D
authors.lastname: Kleindorfer
authors.affiliation: 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.).
authors.forename: Brian
authors.initials: B
authors.lastname: Stettler
authors.affiliation: 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.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Woo
authors.affiliation: 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.).
authors.forename: Pooja
authors.initials: P
authors.lastname: Khatri
authors.affiliation: 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.).
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.affiliation: 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.).
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Pancioli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D002543:Cerebral Hemorrhage / Q000139:chemically induced*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D000077542:Eptifibatide; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D010959:Tissue Plasminogen Activator; D000077542:Eptifibatide
keywords: clinical trial; eptifibatide; stroke; tissue-type plasminogen activator