Renee' H Martin1, Sharon D Yeatts2, Michael D Hill2, Claudia S Moy2, Myron D Ginsberg2, Yuko Y Palesch2. 1. From the Department of Public Health Sciences, Medical University of South Carolina, Charleston (R.H.M., S.D.Y., Y.Y.P.); Calgary Stroke Program, Department of Clinical Neurosciences, Medicine, Radiology and Community Health Sciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, AB, Canada (M.D.H.); Office of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of health, Bethesda, MD (C.S.M.); and Department of Neurology, University of Miami Miller School of Medicine, FL (M.D.G.). hebertrl@musc.edu. 2. From the Department of Public Health Sciences, Medical University of South Carolina, Charleston (R.H.M., S.D.Y., Y.Y.P.); Calgary Stroke Program, Department of Clinical Neurosciences, Medicine, Radiology and Community Health Sciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, AB, Canada (M.D.H.); Office of Clinical Research, National Institute of Neurological Disorders and Stroke, National Institutes of health, Bethesda, MD (C.S.M.); and Department of Neurology, University of Miami Miller School of Medicine, FL (M.D.G.).
Abstract
BACKGROUND AND PURPOSE: The ALIAS (Albumin in Acute Ischemic Stroke) part 1 and 2 trials evaluated whether 25% human serum albumin improves clinical outcomes after acute ischemic stroke above and beyond standard of care using similar protocols. The part 1 trial ended prematurely because of safety concerns, and the part 2 trial terminated early because of futility of finding a statistically significant effect of albumin over saline (control) administration. We combine the subject-level data of the part 1 and 2 trials to reevaluate the efficacy and safety outcomes with the larger sample size. METHODS: The combined data analyses closely follow those conducted in the part 2 trial. The primary outcome is the composite of the modified Rankin Scale and the National Institutes of Health Stroke Scale defined as a composite of modified Rankin Scale score 0 to 1 and National Institutes of Health Stroke Scale score 0 to 1 at 90 days from randomization. The unadjusted analyses use a simple Chi-square test, and those adjusting for baseline covariates use a generalized linear model with log link (to obtain relative risks). RESULTS: The participant characteristics at baseline were generally similar between the treatment groups and between the trials; however, thrombolysis use was greater in part 2 (84% versus 75%), and the upper age limit imposed in part 2 resulted in a younger sample (mean age in part 1 was 69 versus 64 in part 2). In the combined sample, the proportions of good outcome in the 2 treatment groups were identical (41%). Similar results were observed in all secondary efficacy outcomes. Pulmonary edema was a consistent safety concern, with a 6-fold increase in the albumin arm (13%) compared with saline (2%; relative risk =7.76, 95% confidence interval 3.87-15.57). CONCLUSIONS: Treatment with intravenous albumin 25% at 2 g/kg was not associated with improved outcome at 90 days and was associated with increased rates of intracerebral hemorrhage and pulmonary edema. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00235495.
RCT Entities:
BACKGROUND AND PURPOSE: The ALIAS (Albumin in Acute Ischemic Stroke) part 1 and 2 trials evaluated whether 25% human serum albumin improves clinical outcomes after acute ischemic stroke above and beyond standard of care using similar protocols. The part 1 trial ended prematurely because of safety concerns, and the part 2 trial terminated early because of futility of finding a statistically significant effect of albumin over saline (control) administration. We combine the subject-level data of the part 1 and 2 trials to reevaluate the efficacy and safety outcomes with the larger sample size. METHODS: The combined data analyses closely follow those conducted in the part 2 trial. The primary outcome is the composite of the modified Rankin Scale and the National Institutes of Health Stroke Scale defined as a composite of modified Rankin Scale score 0 to 1 and National Institutes of Health Stroke Scale score 0 to 1 at 90 days from randomization. The unadjusted analyses use a simple Chi-square test, and those adjusting for baseline covariates use a generalized linear model with log link (to obtain relative risks). RESULTS: The participant characteristics at baseline were generally similar between the treatment groups and between the trials; however, thrombolysis use was greater in part 2 (84% versus 75%), and the upper age limit imposed in part 2 resulted in a younger sample (mean age in part 1 was 69 versus 64 in part 2). In the combined sample, the proportions of good outcome in the 2 treatment groups were identical (41%). Similar results were observed in all secondary efficacy outcomes. Pulmonary edema was a consistent safety concern, with a 6-fold increase in the albumin arm (13%) compared with saline (2%; relative risk =7.76, 95% confidence interval 3.87-15.57). CONCLUSIONS: Treatment with intravenous albumin 25% at 2 g/kg was not associated with improved outcome at 90 days and was associated with increased rates of intracerebral hemorrhage and pulmonary edema. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00235495.
Authors: Myron D Ginsberg; Yuko Y Palesch; Michael D Hill; Renee H Martin; Claudia S Moy; William G Barsan; Bonnie D Waldman; Diego Tamariz; Karla J Ryckborst Journal: Lancet Neurol Date: 2013-09-27 Impact factor: 44.182
Authors: Myron D Ginsberg; Yuko Y Palesch; Renee H Martin; Michael D Hill; Claudia S Moy; Bonnie D Waldman; Sharon D Yeatts; Diego Tamariz; Karla Ryckborst Journal: Stroke Date: 2010-12-16 Impact factor: 7.914
Authors: Michael D Hill; Renee H Martin; Yuko Y Palesch; Diego Tamariz; Bonnie D Waldman; Karla J Ryckborst; Claudia S Moy; William G Barsan; Myron D Ginsberg Journal: Stroke Date: 2011-05-05 Impact factor: 7.914
Authors: Michael D Hill; Claudia S Moy; Yuko Y Palesch; Renee Martin; Catherine R Dillon; Bonnie Darcy Waldman; Lynn Patterson; Isabel M Mendez; Karla J Ryckborst; Diego Tamariz; Myron D Ginsberg Journal: Int J Stroke Date: 2007-08 Impact factor: 5.266
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Authors: Michael D Hill; Renee H Martin; Yuko Y Palesch; Claudia S Moy; Diego Tamariz; Karla J Ryckborst; Elizabeth B Jones; David Weisman; Creed Pettigrew; Myron D Ginsberg Journal: PLoS One Date: 2015-09-01 Impact factor: 3.240
Authors: Andrea Morotti; Sandro Marini; Umme K Lena; Katherine Crawford; Kristin Schwab; Christina Kourkoulis; Alison M Ayres; M Edip Gurol; Anand Viswanathan; Steven M Greenberg; Christopher D Anderson; Jonathan Rosand; Joshua N Goldstein Journal: J Neurol Date: 2017-03-10 Impact factor: 4.849
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Authors: Soo Young Kim; Vladimir V Senatorov; Christapher S Morrissey; Kristina Lippmann; Oscar Vazquez; Dan Z Milikovsky; Feng Gu; Isabel Parada; David A Prince; Albert J Becker; Uwe Heinemann; Alon Friedman; Daniela Kaufer Journal: Sci Rep Date: 2017-08-09 Impact factor: 4.379