title: A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study.
abstract: BACKGROUND
  The painful episodes of sickle cell disease (SCD) involve vaso-occlusion and impaired oxygen delivery. HBOC-201, a hemoglobin-based oxygen carrier, has been shown to support oxygen delivery in animal studies and to be safe and well tolerated in normal human volunteers. Therefore, we speculated that it might have a therapeutic role in SCD.
  
  
  METHODS
  Eighteen adults with SCD who were asymptomatic at the time of study were enrolled in a Phase I/II single-blind, placebo-controlled, dose-escalation study of HBOC-201. The primary purpose was to assess the safety of the material in this patient population. In addition, as a surrogate marker of efficacy, each subject underwent a variety of exercise tests before and after HBOC-201 was given.
  
  
  RESULTS
  All HBOC-201 infusions were well tolerated by the study subjects and no evidence of toxicity was noted. In addition, there was a significant difference in heart rate response to the identical aerobic exercise workload when the study subjects who received HBOC-201 were compared to the subjects who received placebo (p = 0.0061).
  
  
  CONCLUSIONS
  HBOC-201 was safely administered to patients with SCD who were not in crisis at the time of study. Furthermore, following infusion of the study material, subjects with SCD performed the identical aerobic exercise-induced workload with an increase in heart rate that was significantly less than the increase observed in the subjects who received an infusion of the saline placebo. These safety and surrogate efficacy data support the notion that HBOC-201 could have efficacy as a treatment for the vasoocclusive episodes of SCD.
authors.affiliation: Department of Medicine, Duke-UNC Sickle Cell Center & General Clinical Research Center, University of North Carolina, Chapel Hill 27599-7600, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gonzalez
authors.forename: A C
authors.initials: AC
authors.lastname: Hackney
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: D
authors.initials: D
authors.lastname: Strayhorn
authors.forename: E B
authors.initials: EB
authors.lastname: Hoffman
authors.forename: G
authors.initials: G
authors.lastname: Hughes
authors.forename: E E
authors.initials: EE
authors.lastname: Jacobs
authors.forename: E P
authors.initials: EP
authors.lastname: Orringer
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000503:physiopathology / Q000628:therapy*; D001802:Blood Substitutes / Q000009:adverse effects / Q000627:therapeutic use*; D005080:Exercise Test; D006339:Heart Rate; D006454:Hemoglobins / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D016037:Single-Blind Method
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201