Gonzalez P, Hackney A C, Jones S, Strayhorn D, Hoffman E B, Hughes G, Jacobs E E, Orringer E P
Department of Medicine, Duke-UNC Sickle Cell Center & General Clinical Research Center, University of North Carolina, Chapel Hill 27599-7600, USA.
J Investig Med. 1997 Jun;45(5):258-64.
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.
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.
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).
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.
镰状细胞病（SCD）的疼痛发作涉及血管阻塞和氧输送受损。基于血红蛋白的氧载体HBOC-201在动物研究中已显示可支持氧输送，并且在正常人类志愿者中是安全且耐受性良好的。因此，我们推测它可能在SCD中具有治疗作用。
18名在研究时无症状的成年SCD患者参加了HBOC-201的I/II期单盲、安慰剂对照、剂量递增研究。主要目的是评估该物质在该患者群体中的安全性。此外，作为疗效的替代指标，每个受试者在给予HBOC-201之前和之后都进行了各种运动测试。
研究对象对所有HBOC-201输注耐受性良好，未发现毒性证据。此外，将接受HBOC-201的研究对象与接受安慰剂的对象进行比较时，在相同有氧运动负荷下的心率反应存在显著差异（p = 0.0061）。
在研究时未处于危机状态的SCD患者中安全地给予了HBOC-201。此外，在输注研究材料后，SCD患者进行相同的有氧运动诱导负荷时，心率增加明显小于接受生理盐水安慰剂输注的患者。这些安全性和替代疗效数据支持HBOC-201可能对SCD的血管阻塞发作具有治疗效果的观点。
