Table 3.

Primary and secondary efficacy end points from the EPPIC trials

End PointAST-120PlaceboAST-120 versus Placebo
Nn (%)Nn (%)HR (95% CI)P Values
EPPIC-1
 Primary end pointa
  ITT (censored at last contact)500178 (35.6)502177 (35.3)1.03 (0.84 to 1.27)0.78
  ITT (censored at last sCr)500178 (35.6)502177 (35.3)1.05 (0.86 to 1.30)0.62
  ITT (censored at last sCr)b500159 (31.8)502158 (31.5)1.04 (0.84 to 1.30)0.70
  ITT (90 d lagging censoring)500153 (30.6)502156 (31.1)1.02 (0.81 to 1.27)0.89
  ITT (14 d lagging censoring)500135 (27.0)502133 (26.5)1.06 (0.84 to 1.35)0.61
  PP (censored at last contact)c451156 (34.6)445157 (35.3)1.01 (0.81 to 1.27)0.91
 Secondary end pointd
  ITT (censored at last contact)500213 (42.6)502201 (40.0)1.08 (0.89 to 1.31)0.42
  PP (censored at last contact)451189 (41.9)445177 (39.8)1.08 (0.88 to 1.33)0.44
 Individual end point
  ESRD500161 (32.2)502157 (31.3)1.05 (0.85 to 1.31)0.64
  Doubling of sCr50036 (7.2)50248 (9.6)0.77 (0.50 to 1.19)0.25
  Death50049 (9.8)50242 (8.4)1.17 (0.78 to 1.77)0.45
EPPIC-2
 Primary end pointa
  ITT (censored at last contact)500172 (34.4)497183 (36.8)0.91 (0.74 to 1.12)0.37
  ITT (censored at last sCr)500172 (34.4)497183 (36.8)0.93 (0.75 to 1.15)0.48
  ITT (censored at last sCr)b500156 (31.2)497171 (34.4)0.92 (0.73 to 1.14)0.43
  ITT (90 d lagging censoring)500152 (30.4)497160 (32.2)0.96 (0.76 to 1.20)0.71
  ITT (14 d lagging censoring)500124 (24.8)497140 (28.2)0.89 (0.70 to 1.14)0.37
  PP (censored at last contact)c447155 (34.7)437160 (36.6)0.93 (0.74 to 1.17)0.53
 Secondary end pointd
  ITT (censored at last contact)500204 (40.8)497217 (43.7)0.90 (0.74 to 1.09)0.28
  PP (censored at last contact)447180 (40.3)437190 (43.5)0.90 (0.73 to 1.11)0.34
 Individual end point
  ESRD500146 (29.2)497164 (33.0)0.82 (0.65 to 1.02)0.08
  Doubling of sCr50057 (11.4)49746 (9.3)1.18 (0.80 to 1.74)0.40
  Death50049 (9.8)49761 (12.3)0.78 (0.53 to 1.13)0.19
Pooled
 Primary end pointa
  ITT (censored at last contact)1000350 (35.0)999360 (36.0)0.97 (0.83 to 1.12)0.64
  ITT (censored at last sCr)1000350 (35.0)999360 (36.0)0.98 (0.85 to 1.14)0.79
  ITT (censored at last sCr)b1000315 (31.5)999329 (32.9)0.97 (0.83 to 1.13)0.68
  ITT (90 d lagging censoring)1000305 (30.5)999316 (31.6)0.97 (0.83 to 1.14)0.71
  ITT (14 d lagging censoring)1000259 (25.9)999273 (27.3)0.96 (0.81 to 1.14)0.62
  PP (censored at last contact)c898311 (34.6)882317 (35.9)0.97 (0.83 to 1.14)0.70
 Secondary end pointd
  ITT (censored at last contact)1000417 (41.7)999418 (41.8)0.99 (0.86 to 1.13)0.86
  PP (censored at last contact)898369 (41.1)882367 (41.6)0.99 (0.86 to 1.15)0.92
 Individual end point
  ESRD1000307 (30.7)999321 (32.1)0.93 (0.80 to 1.09)0.37
  Doubling of sCr100093 (9.3)99994 (9.4)0.98 (0.73 to 1.30)0.87
  Death100098 (9.8)999103 (10.3)0.94 (0.71 to 1.24)0.65
  • N, number of patients in the respective population; PP, per protocol.

  • a Primary end point was time to onset of renal disease progression calculated as the time from randomization to the date when the first component of a triple composite end point (initiation of dialysis, kidney transplantation, or doubling of sCr) occurred; the primary analysis was conducted on the ITT (censored at last contact) population. Other analyses on the primary end point were performed to evaluate the robustness of results to censoring patterns.

  • b First occurrence of dialysis, kidney transplantation, or doubling of sCr through 84 days after last sCr assessment or last dose. Patients who did not have an event in this period were censored at last sCr assessment.

  • c PP included all patients in the ITT population who had no major protocol violations or deviations. Blinded data review was conducted before database lock and trial unblinding using detailed criteria, including minimum compliance rate. During the blinded data review, the two major protocol violations that excluded a patient from the PP population were any treatment other than that randomly assigned and treatment compliance rate<67% and/or treatment period<8 weeks.

  • d The secondary end point was time to onset of renal disease progression, calculated as the time from randomization to the date when the first component of a quadruple composite end point (initiation of dialysis, kidney transplantation, doubling of sCr, or death) occurred.