Statistical Analysis.
For the primary endpoint analysis, the following inequality hypothesis were tested: H0: Proportion of responders at 6 months with the MPP feature activated at baseline ≤ 57%; H1: Proportion of responders at 6 months with the MPP feature activated at baseline > 57%. The MPP responder rate was compared to 57%, which is the responder rate obtained from literature13 for patients without the MPP feature activated.
The sample size calculation was based on the primary endpoint, proportion of CRT responders at 6 months who have the MPP feature activated at baseline. Using a one-sided, one sample Exact Binomial Test and a significance level of 2.5%, the study required 74 patients to reach a power of 90%. With the MPP feature activated at baseline, it was assumed that the proportion of responders at 6 months was 75%. In order to detect the 18% difference between the two responder rates, a total of 74 patients was needed to have analyzable endpoint data at 6 months. Assuming that, some patients would drop out of the study, the sample size increased to 103 subjects.
Mean ± standard deviation was reported for continuous data and frequencies and percentage for categorical data. The comparison of numerical variables was performed using Student’s t test or Wilcoxon’s rank-sum test, depending on the distribution of the variables. The Chi squared test, Fisher’s exact test or Wald’s test was used to compare qualitative variables as appropriate. Kaplan-Meier estimates with log-rank tests and multivariable Cox proportional hazards models were used to compare the QUARTO III study participants with the control cohort (Quarto II patients) for patient mortality, hospitalization, and the combined endpoint of mortality and/or hospitalization.