Fig. 3
Statistical testing for the primary and secondary endpoints. For the final analysis, the first hypothesis (non-inferiority of the primary endpoint [3P-MACE]) will be tested at the one-sided alpha-level of 2.5%. In case of significance, the null hypothesis (H0) is rejected in a confirmatory sense and the next set of hypotheses (two separate hypothesis tests) will be tested: (a) test of the primary endpoint for superiority and (b) test of the composite renal endpoint for superiority. To adjust for multiplicity, a sequentially rejective multiple test procedure will be applied. Both one-sided hypotheses H0(Sup1) and H0(Sup2) will be tested separately, at the initial alpha-levels of ×0.2 alpha for the primary endpoint and ×0.8 alpha for the composite renal endpoint, respectively. If both null hypotheses cannot be rejected at these initial alpha-levels, the procedure stops and for neither endpoint can superiority be declared. After having shown superiority for one of these endpoints, the used alpha can be shuffled to the other test: If H0(Sup2) is rejected at the alpha-level of ×0.8 alpha, then H0(Sup1) can be tested at the full alpha-level of 2.5% (one-sided). If H0(Sup1) is rejected at the alpha-level of ×0.2 alpha, then H0(Sup2) can be tested at the full alpha-level of 2.5% (one-sided). *Cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. H 0 null hypothesis, 3P-MACE 3-point major adverse cardiovascular events