Data also suggests the nonionic block polymer surfactant may be harmful for children <16 years of age.
A new study indicates that poloxamer 188 is largely ineffective as a disease-modifying therapy for ongoing painful vaso-occlusive crises in patients with sickle cell disease.
Investigators in a Phase 3 randomized, double-blind, placebo-controlled, multicenter, international trial reevaluated the efficacy of the nonionic block polymer surfactant to confirm findings from previous trials.
The team, led by James Casella, MD, Pediatric Hematology, The Johns Hopkins University School of Medicine, assessed 366 patients across 66 hospitals in 12 countries and 60 cities. All patients presented with hemoglobin SS, SC, S-β0 thalassemia, or S-β+ thalassemia disease, and experienced mild to severe pain from vaso-occlusive crises requiring hospitalization.
The trial was conducted from May 2013-February 2016.
The population included both adults and children; as such, the age range was from 4-65 years, with the mean age being 15.2 years.
Patients first received a 1-hour 100 mg/kg loading dose of poloxamer 188 intravenously. They were then randomized 1:1 to receive 12-to-48-hour 30 mg/kg/h continuous infusion or placebo.
“The primary outcome was hours from randomization until the last administration of parenteral opioid analgesic for painful vaso-occlusive episodes prior to hospital discharge,” the investigators wrote.
“Secondary outcomes included hospitalization for recurrence of painful vaso-occlusive episodes within 14 days of initial hospital discharge and occurrence of acute chest syndrome within 120 hours of randomization.”
The team assessed their defined primary outcome in 384 patients; furthermore, 15-day follow-up was available for 357 patients, and 30-day follow-up was available for 368 patients.
Cassela and team thus reported that—according to analysis of covariance—there was no significant difference between treatment groups in mean time from randomization to last administration of parenteral opioids.
The poloxamer 188 group had a length of 81.8 hours—versus 77.8 hours in the placebo group (difference, 4.0 hours [95% CI, -7.8 to 15.7]; geometric mean ratio, 1.2 [95% CI, 1.0-1.5]; P = .09).
However, the investigators did observe a treatment difference among patients <16 years of age. The mean time for poloxamer patients was 88.7 hours, while the mean time for placebo patients was 71.9 hours (difference, 16.8 [95% CI, 1.7-32.0]; geometric mean ratio, 1.4 [95% CI, 1.1-1.8]; P = .008)
They noted that 32 participants in the entire poloxamer 188 group experienced acute chest syndrome (16.5%), as did 22 in the placebo group (11.3%; difference, 5.2% [95% CI, -1.7 to 12.0]).
Other secondary outcomes showed that 16 of 192 (8.3%) poloxamer 188 patients and 13 of 190 placebo patients (6.8%) were re-hospitalized for recurrence of painful vaso-occlusive episodes within 14 days of therapy administration (difference, 1.5% [95% CI, −3.8% to 6.8%]).
As for adverse events in the poloxamer 188 population, abdominal distension, hepatobiliary disorders (elevated direct or total bilirubin [77.3%]), hyper-bilirubinemia, and upper respiratory infections were most commonly reported.
Conversely, hypoxia and infusion site swelling and pain were more common for those who received placebo.
Severe adverse events were comparable between treatment groups, although anemia was notably more common for placebo patients.
The investigators noted various limitations of their study, including the subjective aspects in relation to perception of pain, the various contributing factors for one’s decision to discontinue opioid use, and the study’s inability to reach full enrollment.
Their findings nonetheless failed to reject the null hypothesis that poloxomer 188 would have no difference in benefit compared to placebo.
“In the current study, there was no evidence of favorable effects of poloxamer 188 on time to last dose of parental opioids,” the team wrote. ”In contrast to the apparent benefit to participants younger than 16 years in the previous phase 3 study, apparent harm with poloxamer 188 was found in this age group in the current study.”
The study, “Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease,” was published online in JAMA.