Statistical Analysis
outcome(s, diabetes
SECONDARY, DIABETES
A statistical analysis plan was agreed by the Trial Management Team and Trial Statistical team prior to analysis. The principle of intention-to-treat was adopted for primary and secondary outcomes, and no interim analysis was planned. Analyses included all randomised participants for whom the outcome(s) of interest (and any covariates) were available. Categorical data are presented using counts and percentages. Continuous data are presented as mean (standard deviation) and median (Quartile 1, Quartile 3) for normally and non-normally distributed variables, respectively. Primary and secondary clinical outcomes were calculated as the within group difference in measurements obtained at the baseline visit (Visit 1) and end of treatment (Visit 3) and presented as the absolute difference and standardised difference (divided by the number of days between visits). An exploratory analysis investigated the between group difference in all cardiovascular outcomes between baseline (Visit 1) and end of treatment (Visit 3) using standard analysis of covariance with the baseline measurement, treatment allocation and days between visits included as covariates.A number of post hoc analyses are included here which were not included in the original statistical analysis plan. These include systolic BP, pregnancy outcomes and longitudinal measurement of BP, uterine artery and angiogenic markers after treatment cessation in routine clinical visits in the translational research clinic. In addition, analysis of the arginine, L-citrulline and ADMA measurements and the relationship of these measurements to cardiovascular parameters and compliance were a post hoc analysis. All post hoc analyses were performed by the research team (JEM), not the Liverpool Clinical Trial Centre statistician. Reporting of the incidence of pre-existing diabetes, parity and baseline antihypertensive use within the study population was not pre-specified.