This study was done to better understand treatment risks and benefits of drotrecogin alfa (activated) (DrotAA).
A blinded, independent clinical evaluation committee evaluated all serious adverse events (SAEs) within INDEPTH, a 4459 patient integrated database of five clinical trials of patients with severe sepsis. Trials were conducted by a single sponsor (Eli Lilly and Company). We report the incidence of cardiac serious adverse events in placebo treated patients (n=1231) and in those treated with DrotAA (n=3228).
SAEs were characterized as occurring either during the study drug infusion period or during the 28-day survival observation period. Sepsis-related clinical outcomes and sepsis-related deaths were not considered SAEs unless attributable to study drug. Despite higher survival in DrotAA, overall SAEs rates were similar in both groups. Observed rates for MI and arrhythmia were significantly lower during infusion period and at 28 days.
These data show a possible association between DrotAA administration and a reduced rate of cardiac events in patients with severe sepsis.
Further investigation may be justified.
Table 1VariableDrotAA N=3228Placebo N=1231p Value*Infusion Period: All SAE: N (%)199 (6.2%)78 (6.3%)NSAll bleeding Arrhythmia w/o MI37 (1.15%)30 (2.44%)0.0015All non bleedingMyocardial Infarction11 (0.34%)10 (0.81%)0.04Death at 28 Days following any Infusion Period SAE87/199 (43.7%)†47/78 (60.3%)†0.013MI/Thrombotic All stroke/ other arterial thrombotic events28 Day Observation Period: All SAE: N (%)425 (13.2%)170 (13.8%)NSArrhythmia w/o MI54 (1.67%)43 (3.49%)<0.001Arrhythmia without MIMyocardial Infarction17 (0.53%)15 (1.22%)0.0140ther ? Death at 28 days YesDeath at 28 Days following any SAE137/425 (32.2%)†72/170 (42.4.3%)†0.02†
In these rows only, the denominator for the calculation of percentage mortality is the number of patients at that time point with an SAE.
Darell Heiselman, Consultant fee, speaker bureau, advisory committee, etc. Advisory panel fee. Table 1