A phase I/II study of polymerized bovine hemoglobin in adult patients with sickle cell disease not in crisis at the time of study
Journal of Investigative Medicine. 1997;45((5):):258-64.
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.
Perfluorocarbons as blood substitutes: the early years. Experience with Fluosol DA-20% in the 1980s
Artificial Cells, Blood Substitutes, & Immobilization Biotechnology. 1994;22((4):):955-63.
Clinical testing of perfluorocarbons (PFC) as blood substitutes began in the early 1980's in the form of Fluosol DA-20% (FDA), a mixture of perfluorodecalin and perfluorotripropylamine emulsified with Pluronic F68. We have treated 55 patients (Treatment (T) = 40; Control (C) = 15) with intravenous infusions of 30 cc/kg of FDA as part of either a randomized, clinical trial or a humanitarian protocol. All patients were Jehovah's Witnesses who refused blood transfusion and were severely anemic (mean hemoglobin = 4.6 g/d). FDA successfully increased dissolved or plasma oxygen content (P1O2 in ml/dl), but not overall oxygen content (T group: P1O2 baseline = 1.01 +/- .27, P1O2 12hrs = 1.58 +/- .47 [p = < .0001, t-test]; P1O2 12 hrs: T = 1.58 +/- .47, C = 1.00 +/- .31, p = < .0002, t-test). This effect persisted for only 12 hours post infusion, and had no apparent effect on survival. FDA is an ineffective blood substitute because of low concentration and short half-life. Improved emulsion design may resolve these problems, thereby producing a more effective agent. Our discussion will include a review of our data plus a summary of other reports of FDA efficacy as a blood substitute. [References: 13]
Fluosol DA-20 in the treatment of severe anemia: randomized, controlled study of 46 patients
Critical Care Medicine. 1990;18((11):):1227-30.
We evaluated the safety and efficacy of Fluosol DA-20% (FDA) as a blood substitute in the treatment of severe anemia. Thirty-six patients received either FDA (n = 21) or crystalloid/hydroxyethyl starch (CHS) (n = 15) as part of a randomized, controlled trial. Ten patients received FDA as part of a humanitarian protocol. All were Jehovah's Witnesses who refused transfusion, had bled recently, and had average Hgb levels of 4.3 g/dl. After pulmonary artery catheter insertion, each patient was infused with CHS to attain a pulmonary artery wedge pressure (WP) of 10 to 18 mm Hg. FDA was given as a one-time dose of 30 ml/kg. Data were collected at baseline, 12, 24, and 48 h. None of the patients with negative reactions to a 0.5-ml test dose of FDA had adverse reactions to the subsequent infusion. The plasma or dissolved component of oxygen content was significantly higher in the FDA group at 12 h (FDA group 1.58 +/- 0.47 ml/dl, control group 1.01 +/- 0.31 ml/dl, p less than .02, t-test). Nineteen patients died: 12 (37.5%) FDA, seven (46.6%) control. The difference was not significant. We conclude the following: a) FDA can be given safely to severely anemic patients in doses of 30 ml/kg; b) FDA significantly increased the dissolved component of oxygen content after 12 h but the effect did not persist; c) severely anemic patients can survive without transfusion although mortality is high. In this study, inability of FDA to sustain increased oxygen content was due in part to the rapid elimination of FDA and also to the limited amount given.(ABSTRACT TRUNCATED AT 250 WORDS)