Adams-Graves P, Kedar A, Koshy M, Steinberg M, Veith R, Ward D, Crawford R, Edwards S, Bustrack J, Emanuele M
University of Tennessee, Memphis 38163, USA.
Blood. 1997 Sep 1;90(5):2041-6.
RheothRx (Glaxo Wellcome Inc, Research Triangle Park, NC; poloxamer 188) Injection is a nonionic surfactant with hemorrheologic properties that suggest it may be useful in treating acute painful episodes (vasoocclusive crises) of sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of poloxamer, formulated as RheothRx Injection, in 50 patients with SCD. Patients with moderate to severe painful episodes requiring parenteral analgesics were randomized to receive a 48-hour infusion of either RheothRx or placebo. Pain was assessed every 4 hours. Efficacy endpoints included: (1) painful episode duration, (2) days of hospitalization, (3) quantity of analgesics used, and (4) pain intensity scores. Three subgroups of patients were considered for efficacy analyses based on the actual duration of the study drug infusion and the completeness of pain score data collection. Compared with placebo and depending on the subgroup, RheothRx-treated patients showed a 16% to 45% decrease in duration of painful episodes, a 1- to 2-day reduction in hospital stay, a threefold to fivefold reduction in analgesic requirements, and a 1-point reduction (using a 5-point scale) in average pain intensity scores at 72 hours. RheothRx was well tolerated; no clinically significant differences were observed between treatments with respect to adverse experiences or other safety measures. In addition, there were no differences between treatment groups in the incidence of recurrent painful episodes. In this study, RheothRx significantly reduced total analgesic use and pain intensity and showed trends to shorter duration of painful episodes and total days of hospitalization. In patients with moderate to severe vasoocclusive pain, RheothRx was safe and may offer a therapeutic benefit.
流变素（葛兰素威康公司，北卡罗来纳州三角研究园；泊洛沙姆188）注射液是一种具有血液流变学特性的非离子表面活性剂，提示其可能有助于治疗镰状细胞病（SCD）的急性疼痛发作（血管阻塞性危象）。我们进行了一项随机、双盲、安慰剂对照的试点研究，以评估制成流变素注射液的泊洛沙姆在50例SCD患者中的安全性和有效性。需要胃肠外镇痛的中度至重度疼痛发作患者被随机分配接受48小时的流变素或安慰剂输注。每4小时评估一次疼痛情况。疗效终点包括：（1）疼痛发作持续时间，（2）住院天数，（3）使用的镇痛药数量，以及（4）疼痛强度评分。根据研究药物输注的实际持续时间和疼痛评分数据收集的完整性，将患者分为三个亚组进行疗效分析。与安慰剂相比，根据亚组不同，接受流变素治疗的患者疼痛发作持续时间减少了16%至45%，住院时间缩短了1至2天，镇痛药需求量减少了三至五倍，72小时时平均疼痛强度评分（采用5分制）降低了1分。流变素耐受性良好；在不良经历或其他安全措施方面，各治疗组之间未观察到临床显著差异。此外，治疗组之间复发性疼痛发作的发生率没有差异。在本研究中，流变素显著减少了镇痛药的总用量和疼痛强度，并显示出疼痛发作持续时间和总住院天数缩短的趋势。对于中度至重度血管阻塞性疼痛患者，流变素是安全的，可能具有治疗益处。
