naa a22 4500 510799671 CHVBK 20180411083349.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s12028-013-9861-y doi (NATIONALLICENCE)springer-10.1007/s12028-013-9861-y High Dose Deferoxamine in Intracerebral Hemorrhage (H i -D ef ) Trial: Rationale, Design, and Methods [Elektronische Daten] [Sharon Yeatts, Yuko Palesch, Claudia Moy, Magdy Selim] Background: Hemoglobin degradation products, in particular iron, have been implicated in secondary neuronal injury following intracerebral hemorrhage (ICH). The iron chelator Deferoxamine Mesylate (DFO) exerts diverse neuroprotective effects, reduces perihematoma edema (PHE) and neuronal damage, and improves functional recovery after experimental ICH. We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a Phase I, open-label study to determine the tolerability, safety, and maximum tolerated dose (MTD) of DFO in patients with ICH. Intravenous infusions of DFO in doses up to 62mg/kg/day (up to a maximum of 6000mg/day) were well-tolerated and did not seem to increase serious adverse events (SAEs) or mortality. We have initiated a multi-center, double-blind, randomized, placebo-controlled, Phase II clinical trial (High Dose Deferoxamine [HI-DEF] in Intracerebral Hemorrhage) to determine if it is futile to move DFO forward to Phase III efficacy evaluation. Methods: We will randomize 324 subjects with spontaneous ICH to either DFO at 62mg/kg/day (up to a maximum daily dose of 6000mg/day) or saline placebo, given by intravenous infusion for 5 consecutive days. Treatment will be initiated within 24 hours after ICH symptom onset. All subjects will be followed for 3 months and will receive standard of care therapy while participating in the study. At 3 months, the proportion of DFO-treated subjects with a good clinical outcome, assessed by modified Rankin Scale, will be compared to the placebo proportion in a futility analysis. Conclusions: The Hi-Def trial is expected to advance our understanding of the pathopgysiology of secondary neuronal injury in ICH and will provide a crucial "Go/No Go” signal as to whether a Phase III trial to investigate the efficacy of DFO is warranted. Springer Science+Business Media New York, 2013 Intracerebral hemorrhage nationallicence Deferoxamine nationallicence Clinical trial nationallicence Futility design nationallicence Yeatts Sharon Data Coordination Unit, Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA aut Palesch Yuko Data Coordination Unit, Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA aut Moy Claudia National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA aut Selim Magdy Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Palmer 127, 02215, Boston, MA, USA aut Neurocritical Care Springer US; http://www.springer-ny.com 19/2(2013-10-01), 257-266 1541-6933 19:2<257 2013 19 12028 https://doi.org/10.1007/s12028-013-9861-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12028-013-9861-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yeatts Sharon Data Coordination Unit, Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA aut NATIONALLICENCE 700 1- Palesch Yuko Data Coordination Unit, Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA aut NATIONALLICENCE 700 1- Moy Claudia National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Selim Magdy Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Palmer 127, 02215, Boston, MA, USA aut NATIONALLICENCE 773 0- Neurocritical Care Springer US; http://www.springer-ny.com 19/2(2013-10-01), 257-266 1541-6933 19:2<257 2013 19 12028 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer