Statistical Analysis
Analyses were conducted with SAS® software (version 9.4.). The primary analysis was performed with the intention-to-treat (ITT) set, i.e. all randomized patients who received at least one dose of IMP. The primary endpoint was analysed using a logistic regression model with adjustments for treatment, baseline fibrinogen levels (categorized as ≤ 2, ]2;3], ]3,4], > 4 g/L) and centre (23 centres that enrolled less than 20 patients were pooled as one centre). The treatment effect was estimated as an odds ratio (OR) along with its 95% Confidence Interval (95%CI) and tested with the Wald test at the 0.05 significance level. An OR below 1 indicated a lower failure risk in the fibrinogen group compared to the control group. Missing data were not replaced in the primary analysis. Sensitivity analyses for handling missing data were performed. Another supportive analysis was performed on the per-protocol (PP) set.
Changes in plasma fibrinogen levels from IMP administration to 2 hours (H2), 6 hours (H6) and 2 days (D2) were analysed in a Mixed Model for Repeated Measurements (MMRM). For continuous secondary efficacy endpoints, treatment groups were compared with a t-test or a Wilcoxon test, and binary endpoints were compared with a Pearson Chi-square test or a Fisher exact test. All p-values provided for secondary efficacy endpoints are for exploratory purposes only. No adjustments were made for multiple comparisons.