title: Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage.
abstract: OBJECTIVE
  Treatment with the iron chelator, deferoxamine mesylate (DFO), improves neurological recovery in animal models of intracerebral hemorrhage (ICH). We aimed to evaluate the feasibility, safety, and tolerability of varying dose-tiers of DFO in patients with spontaneous ICH, and to determine the maximum tolerated dose to be adopted in future efficacy studies.
  
  
  METHODS
  This was a multicenter, phase-I, dose-finding study using the Continual Reassessment Method. DFO was administered by intravenous infusion for 3 consecutive days, starting within 18 hours of ICH onset. Subjects underwent repeated clinical assessments through 90 days, and computed tomography neuroimaging pre- and post-drug-administration.
  
  
  RESULTS
  Twenty subjects were enrolled onto 5 dose tiers, starting with 7 mg/kg per day and ending with 62 mg/kg per day as the maximum tolerated dose. Median age was 68 years (range, 50-90); 60% were men; and median Glasgow Coma Scale and National Institutes of Health Stroke Scale scores on admission were 15 (5-15) and 9 (0-39), respectively. ICH location was lobar in 40%, deep in 50%, and brain stem in 10%; intraventricular hemorrhage was present in 15%. DFO was discontinued because of adverse events in 2 subjects (10%). Six subjects (30%) experienced 12 serious adverse events, none of which were drug-related. DFO infusions were associated with mild blood-pressure-lowering effects. Fifty percent of patients had modified Rankin scale scores ≤2, and 39% had modified Rankin scale scores of 4 to 6 on day 90; 15% died.
  
  
  CONCLUSIONS
  Consecutive daily infusions of DFO after ICH are feasible, well-tolerated, and not associated with excessive serious adverse events or mortality. Our findings lay the groundwork for future studies to evaluate the efficacy of DFO in ICH.
authors.affiliation: Department of Neurology, Stroke Division, Beth Israel Deaconess Medical Center, Stroke Division, 330 Brookline Avenue-Palmer 127, Boston, MA 02215, USA. mselim@bidmc.harvard.edu
authors.forename: Magdy
authors.initials: M
authors.lastname: Selim
authors.forename: Sharon
authors.initials: S
authors.lastname: Yeatts
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Goldstein
authors.forename: Joao
authors.initials: J
authors.lastname: Gomes
authors.forename: Steven
authors.initials: S
authors.lastname: Greenberg
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Morgenstern
authors.forename: Gottfried
authors.initials: G
authors.lastname: Schlaug
authors.forename: Michel
authors.initials: M
authors.lastname: Torbey
authors.forename: Bonnie
authors.initials: B
authors.lastname: Waldman
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Palesch
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D003676:Deferoxamine / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
chemical_list: D003676:Deferoxamine