Poloxamer 188 does not decrease vaso-occlusive episodes in sickle cell disease: JAMA

The study is published in the JAMA Network.

A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in sickle cell disease, particularly in children and participants treated with hydroxyurea.

Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive.

Hence, James F. Casella and colleagues from the Johns Hopkins University School of Medicine, Baltimore, Maryland conducted the present study to reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.

The researchers carried out a phase 3, randomized, double-blind, placebo-controlled, multicenter, international trial 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.

A 1-hour 100-mg/kg loading dose of poloxamer 188 was administered intravenously followed by a 12-hour to 48-hour 30-mg/kg/h continuous infusion (n = 194) or placebo (n = 194). Time in hours from randomization to the last dose of parenteral opioids among all participants was evaluated and among those younger than 16 years as a separate subgroup was analyzed.

The results showed that-

5. 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%).
6. 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).
7. 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).
8. 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%).

Therefore, the authors concluded that "among children and adults with sickle cell disease, 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."