Table 2.

Occurrence of the adjudicated primary composite outcome of doubling of serum creatinine, ESRD, or death and its individual components and of secondary outcomes

ParameterAvosentan 25 mg (n = 455)Avosentan 50 mg (n = 478)Placebo (n = 459)P
Avosentan 25 mg versus placeboAvosentan 50 mg versus placebo
Primary composite outcome37 (8.1)41 (8.6)44 (9.6)0.5570.791
    death21 (4.6)a17 (3.6)12 (2.6)0.2250.194
    ESRD20 (4.4)24 (5.0)30 (6.5)0.1360.405
    doubling of serum creatinine2 (0.4)4 (0.8)9 (2.0)0.4050.060
Cardiovascular outcome68 (14.9)71 (14.9)47 (10.2)0.0490.089
    CHF27 (5.9)29 (6.1)10 (2.2)0.0080.050
  • All events were adjudicated and are n (%). The cardiovascular outcome was defined as the composite of coronary or peripheral vascular revascularization, amputations (except from trauma), nonfatal acute myocardial infarction, stroke, and CHF. Of 66 patients with CHF (typical signs and/or symptoms of CHF and having received new therapy for CHF and being admitted to hospital for at least 24 hours), 49 occurred in those with baseline eGFR below the median of 33 ml/min per 1.73 m2.

  • aFor death in the avosentan 25-mg group, we added four deaths that were reported after closure of the trial and discontinuation of trial medication and could not be adjudicated because of insufficient information; there were 17 adjudicated deaths in that group. Excluding those four deaths did not materially alter the difference to placebo (P = 0.313).