Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.
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Casella James F, Barton Bruce A, Kanter Julie, Black L Vandy, Majumdar Suvankar, Inati Adlette, Wali Yasser, Drachtman Richard A, Abboud Miguel R, Kilinc Yurdanur, Fuh Beng R, Al-Khabori Murtadha K, Takemoto Clifford M, Salman Emad, Sarnaik Sharada A, Shah Nirmish, Morris Claudia R, Keates-Baleeiro Jennifer, Raj Ashok, Alvarez Ofelia A, Hsu Lewis L, Thompson Alexis A, Sisler India Y, Pace Betty S, Noronha Suzie A, Lasky Joseph L, de Julian Elena Cela, Godder Kamar, Thornburg Courtney Dawn, Kamberos Natalie L, Nuss Rachelle, Marsh Anne M, Owen William C, Schaefer Anne, Tebbi Cameron K, Chantrain Christophe F, Cohen Debra E, Karakas Zeynep, Piccone Connie M, George Alex, Fixler Jason M, Singleton Tammuella C, Moulton Thomas, Quinn Charles T, de Castro Lobo Clarisse Lopes, Almomen Abdulkareem M, Goyal-Khemka Meenakshi, Maes Philip, Emanuele Marty, Gorney Rebecca T, Padgett Claire S, Parsley Ed, Kronsberg Shari S, Kato Gregory J, Gladwin Mark T
Аннотация
OBJECTIVE: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.
DESIGN, SETTING, AND PARTICIPANTS: Phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial conducted from May 2013 to February 2016 that included 66 hospitals in 12 countries and 60 cities; 388 individuals with SCD (hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease) aged 4 to 65 years with acute moderate to severe pain typical of painful vaso-occlusive episodes requiring hospitalization were included.
INTERVENTIONS: A 1-hour 100-mg/kg loading dose of poloxamer 188 intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194).
MAIN OUTCOMES AND MEASURES: Time in hours from randomization to the last dose of parenteral opioids among all participants and among those younger than 16 years as a separate subgroup.
RESULTS: Of 437 participants assessed for eligibility, 388 were randomized (mean age, 15.2 years; 176 [45.4%] female), the primary outcome was available for 384 (99.0%), 15-day follow-up contacts were available for 357 (92.0%), and 30-day follow-up contacts were available for 368 (94.8%). There was no significant difference between the groups for the mean time to last dose of parenteral opioids (81.8 h for the poloxamer 188 group vs 77.8 h for the placebo group; difference, 4.0 h [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09). Based on a significant interaction of age and treatment (P = .01), there was a treatment difference in time from randomization to last administration of parenteral opioids for participants younger than 16 years (88.7 h in the poloxamer 188 group vs 71.9 h in the placebo group; difference, 16.8 h [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008). Adverse events that were more common in the poloxamer 188 group than the placebo group included hyperbilirubinemia (12.7% vs 5.2%); those more common in the placebo group included hypoxia (12.0% vs 5.3%).
CONCLUSIONS AND RELEVANCE: Among children and adults with SCD, poloxamer 188 did not significantly shorten time to last dose of parenteral opioids during vaso-occlusive episodes. These findings do not support the use of poloxamer 188 for vaso-occlusive episodes.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01737814.