Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis

Table 4 Summary of adverse events by sequence of enrollment (ADDRESS)

Variable	Drotrecogin alfa (activated)			Placebo
	≤2nd patient (n = 459)	≥3rd patient (n = 858)	P value	≤2nd patient (n = 422)	≥3rd patient (n = 851)	P value
Patients with ≥1 SBE	16 (5.5%)	35 (4.1%)	0.60	11 (2.5%)	17 (2.0%)	0.57
Patients with ≥1 SBE during infusion	9 (2.0%)	22 (2.6%)	0.49	6 (1.4%)	9 (1.1%)	0.63
Patients with ≥1 BE	61 (13.3%)	82 (9.6%)	0.04	33 (7.5%)	50 (5.9%)	0.27
Patients with ≥1 of any BE during infusion	53 (11.5%)	69 (8.0%)	0.04	28 (6.3%)	41 (4.8%)	0.25
Patients requiring any blood transfusion	38 (8.3%)	52 (6.1%)	0.13	19 (4.3%)	25 (2.9%)	0.20
Patients with ≥1 BE and who did not survive	28 (6.1%)	29 (3.4%)	0.02	7 (1.7%)	16 (1.9%)	0.68

'≤2nd patient' refers to the first two patients enrolled. '≥3rd patient' refers to the third and subsequent patients enrolled. Frequencies were analyzed using a chi-square test. ADDRESS, ADministration of DRotrecogin alfa (activated) in Early Stage Severe Sepsis; BE, bleeding event reported as an adverse event; SBE, bleeding event reported as a serious adverse event.