• Statistical analysis plan: Analysis was performed for the intent-to-treat population. Chi-square test was used comparison among study groups for categorical data. For continuous outcomes, one-way ANOVA was used for between-group comparison, followed by multiple comparison with Bonferroni adjustment. Paired t-test was used for pre-post comparison within each study group. Non-parametric methods were used for non-normal data, data with unequal variances. The analysis was completed using the statistical package SPSS17.0.