Table 2. Outcomes in a Study of the Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Diseasea,b.
| Outcome | Poloxamer 188 | Placebo | Difference (95% CI) | Least squares geometric mean ratio (95% CI)c | P valued |
|---|---|---|---|---|---|
| Primary outcome | |||||
| Time from randomization to last administration of parenteral opioids for treatment of vaso-occlusive episodes, mean, h | |||||
| Primary analysis population | 81.8 (n = 194) | 77.8 (n = 194) | 4.0 (−7.8 to 15.7) | 1.2 (1.0 to 1.5) | .09 |
| Participants aged <16 y | 88.7 (n = 115) | 71.9 (n = 112) | 16.8 (1.7 to 32.0) | 1.4 (1.1 to 1.8) | .008 |
| Participants aged ≥16 y | 71.7 (n = 79) | 86.0 (n = 82) | −14.3 (−32.8 to 4.3) | 0.9 (0.7 to 1.4) | .76 |
| Secondary outcomes, No./total No. (%) | |||||
| Acute chest syndrome | 32/194 (16.5) | 22/194 (11.3) | 5.2 (−1.7 to 12.0) | ||
| Re-hospitalization for recurrence of vaso-occlusive episodes within 14 d of initial hospital discharge | 16/192 (8.3) | 13/190 (6.8) | 1.5 (−3.8 to 6.8) | ||
All primary analysis population results are shown. Only prespecified subgroups for which interaction testing was significant are shown. The interaction between treatment and age was significant (P = .01). Interactions between treatment and other subgroups of interest, including hydroxyurea usage and region, were tested and found to be not significant (P = .51 and P = .87). All other nonsignificant prespecified analyses are shown in eTables 3, 4, and 5 in Supplement 3.
Comparisons between treatment groups in the primary efficacy analysis were adjusted for age (<16, ≥16), hydroxyurea use (yes, no), Wong-Baker FACES Pain Rating Scale score at randomization (<8, ≥8), and region (US, non-US) in an analysis of covariance model. Secondary outcome comparisons between treatment arms were adjusted for the same variables, using logistic regression.
For the primary outcome, the natural log transformation was applied to individual values prior to conducting each analysis. The least squares means and least squares mean differences were calculated on a log scale and transformed back to the original scale using the exponential function to obtain geometric means and geometric mean ratios. The least squares geometric mean ratio is an indication of the difference between the log mean time for poloxamer 188 and placebo adjusted for other factors in the model. A CI that does not include 1.0 indicates a significant difference.
Computed using a geometric analysis of covariance test.