Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial.

CONTEXT: Sickle cell disease (SCD) can cause severe painful episodes that are often thought to be caused by vaso-occlusion. The current therapy for these uncomplicated painful episodes includes hydration, oxygen, and analgesics. Purified poloxamer 188 may increase tissue oxygenation and thereby reduce inflammation, pain, and the overall duration of such painful episodes in patients with SCD. OBJECTIVE: To compare the duration of painful episodes in patients with SCD treated with purified poloxamer 188 to that of similar episodes experienced by patients who receive a placebo. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled, intention-to-treat trial conducted between March 1998 and October 1999 in 40 medical centers in the United States. PARTICIPANTS: Two hundred fifty-five patients with SCD (aged 9-53 years) who had a painful episode sufficiently severe to require hospitalization and narcotic analgesics. INTERVENTION: Patients were randomly assigned to receive an intravenous infusion of purified poloxamer 188, 100 mg/kg for 1 hour followed by 30 mg/kg per hour for 47 hours (n = 127), or a matching volume of saline placebo (n = 128). MAIN OUTCOME MEASURE: Duration of the painful episode, from randomization to crisis resolution. RESULTS: Mean (SD) duration of the painful episodes was 141 (42) hours in the placebo group compared with 133 (41) hours in those treated with purified poloxamer 188, a 9-hour reduction (P =.04). Subset analyses indicated an even more pronounced purified poloxamer 188 effect in children aged 15 years or younger (21 hours; P =.01) and in patients who were receiving hydroxyurea (16 hours; P =.02). Finally, the proportion of patients achieving crisis resolution was increased by purified poloxamer 188 (65/126 [52%] vs 45/123 [37%]; P =.02). Similar results were observed in children aged 15 years or younger (22/37 [60%] vs 10/36 [28%]; P =.009) and in patients who were also receiving hydroxyurea (12/26 [46%] vs 4/28 [14%]; P =.02). CONCLUSIONS: A decrease in the duration of painful episodes and an increase in the proportion of patients who achieved resolution of the symptoms were observed when the purified poloxamer 188-treated patients were compared with the patients receiving placebo. However, the difference between these groups was significant but relatively small. In subgroup analysis, a more significant effect on both parameters was observed in children and in patients who were receiving concomitant hydroxyurea. It is important to confirm both of these observations in further prospective trials.

RheothRx (poloxamer 188) injection for the acute painful episode of sickle cell disease: a pilot study.

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.