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Purified Poloxamer 188 for Treatment of Acute Vaso-occlusive Crisis of Sickle Cell Disease
A Randomized Controlled Trial
Eugene P. Orringer, MD;
James F. Casella, MD;
Kenneth I. Ataga, MD;
Mabel Koshy, MD;
Patricia Adams-Graves, MD;
Lori Luchtman-Jones, MD;
Ted Wun, MD;
Masayo Watanabe, MD;
Frank Shafer, MD;
Abdullah Kutlar, MD;
Miguel Abboud, MD;
Martin Steinberg, MD;
Brian Adler, MD;
Paul Swerdlow, MD;
Carol Terregino, MD;
Suzanne Saccente, MD;
Beatrice Files, MD;
Samir Ballas, MD;
Robert Brown, PhD;
Slawomir Wojtowicz-Praga, MD;
J. Michael Grindel, MD
JAMA. 2001;286:2099-2106.
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.
Author Affiliations: University of North Carolina at Chapel Hill (Drs Orringer and Ataga); Johns Hopkins University School of Medicine, Baltimore, Md (Dr Casella); University of Illinois at Chicago Medical Center (Dr Koshy); University of Tennessee Medical Center, Memphis (Dr Adams-Graves); St Louis Children's Hospital, St Louis, Mo (Dr Luchtman-Jones); University of California, Davis, School of Medicine, Sacramento (Dr Wun); Children's Mercy Hospital, Kansas City, Mo (Dr Watanabe); St Christopher's Hospital for Children, Philadelphia, Pa (Dr Shafer); Medical College of Georgia, Augusta (Dr Kutlar); Medical University of South Carolina, Charleston (Dr Abboud); University of Mississippi Medical Center, Jackson (Dr Steinberg); University of Alabama at Birmingham Medical Center (Dr Adler); Harper Hospital, Detroit, Mich (Dr Swerdlow); University of Medicine and Dentistry New Jersey–Robert Wood Johnson Medical School, New Brunswick (Dr Terregino); Arkansas Children's Hospital, Little Rock (Dr Saccente); East Carolina University Medical Center, Greenville, NC (Dr Files); Jefferson Medical College, Philadelphia, Pa (Dr Ballas); Theradex, Princeton, NJ (Dr Wojtowicz-Praga); and CytRx Corp, Norcross, Ga (Dr Grindel). Dr Steinberg is now with Boston University School of Medicine, Boston, Mass. Dr Files is now with Children's Healthcare of Atlanta, Atlanta, Ga. Dr Brown is an independent statistician in Colmar, Pa.
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