Table 2.
28-Day all-cause mortality by study and by selected subgroups
| Molecule | Study type (n) | Patient population | Placebo mortality (% [n]) | Treatment mortality (% [n]) |
| PAFase (Opal et al. 2004) [28] | Severe sepsis (1,261) | Primary | 24% (150/618) | 25% (161/643) |
| APACHE II score: | ||||
| <16 | 13% (16/122) | 11% (16/146) | ||
| 16–20 | 21% (31/151) | 19% (30/158) | ||
| 21–25 | 22% (35/156) | 25% (44/173) | ||
| >25 | 36% (68/188) | 43% (70/162) | ||
| TFPI (Abraham et al. 2003) [29] | Severe sepsis (1,955) | All patients | 33% (323/992) | 32% (311/963) |
| Primary: | ||||
| INR ≥ 1.2 | 34% (296/874) | 34% (301/880) | ||
| INR <1.2 | 23% (27/118) | 12% (10/83) | ||
| Shock and INR ≥ 1.2: | ||||
| Yes | 35% (234/666) | 36% (231/635) | ||
| No | 30% (62/208) | 29% (70/245) | ||
| APACHE II score and INR ≥ 1.2: | ||||
| <20 | 22% (45/207) | 18% (33/188) | ||
| ≥20 | 37% (249/665) | 39% (267/689) | ||
| Low-dose steroids (Annane et al. 2002) [27] | Septic shock (299) | All patients | 61% (91/149) | 55% (82/150) |
| Primary: | ||||
| Nonresponder to corticotropin stimulation test | 63% (73/115) | 53% (60/114) | ||
| Responder | 53% (18/34) | 61% (22/61) | ||
| ATIII (Warren et al. 2001) [35] | Severe sepsis (2,314) | Primary | 39% (448/1,157) | 39% (449/1,157) |
| Shock: | ||||
| Yes (n = 1,118) | 43% | 44% | ||
| No (n = 1,191) | 35% | 34% | ||
| SAPS II score: | ||||
| <30% (n = 652) | 19% | 22% | ||
| 30–60% (n = 1,008) | 41% | 37% | ||
| >60% (n = 654) | 55% | 59% | ||
| Ibuprofen (Bernard et al. 1997) [44] | Severe sepsis (455) | Primary | 40% (92/231) | 37% (83/224) |
| Shock: | ||||
| Yes | 45% (66/147) | 42% (61/146) | ||
| No | 31% (26/84) | 28% (22/78) | ||
| IL-1ra (1st phase III) 1 mg/kg per hour (Fisher et al. 1994 [32]; Knaus et al. 1996 [6]) | Severe sepsis (600) | Low dose | 34% (102/302) | 31% (91/298) |
| Shock: | ||||
| Yes | 36% (85/239) | 31% (76/244) | ||
| No | 27% (17/63) | 28% (15/54) | ||
| Predicted risk for death: | ||||
| ≥24% | 45% (85/189) | 38% (72/192) | ||
| <24% | 15% (17/113) | 18% (19/106) | ||
| Organ dysfunctions at baseline: | ||||
| None | 19% (22/115) | 13% (14/105) | ||
| 1 or more | 43% (80/187) | 40% (77/193) | ||
| IL-1ra (1st phase III) 2 mg/kg per hour (Fisher et al. 1994) [32] | Severe sepsis (595) | High dose | 34% (102/302) | 29% (86/293) |
| Shock: | ||||
| Yes | 36% (85/239) | 31% (71/230) | ||
| No | 27% (17/63) | 24% (15/63) | ||
| Predicted risk of death | ||||
| ≥24% | 45% (85/189) | 35% (70/199) | ||
| <24% | 15% (17/113) | 17% (16/94) | ||
| Organ dysfunctions at baseline: | ||||
| None | 19% (22/115) | 24% (26/110) | ||
| 1 or more | 43% (80/187) | 33% (60/183) | ||
| IL-1ra (2nd phase III) 2 mg/kg per hour (Opal et al. 1997) [34] | Severe sepsis (906) | Primary | 36% | 34% |
| Evaluable | 36% (126/346) | 33.1% (116/350) | ||
| Predicted risk for death | ||||
| ≤24% (n = 461) | 42% | 42% | ||
| <24% (n = 235) | 24% | 18% | ||
| Organ dysfunctions at baseline: | ||||
| None | 24% (22/91) | 18% (17/93) | ||
| Single | 36% (47/132) | 32% (43/134) | ||
| Multiple | 46% (57/123) | 46% (56/123) | ||
| ARDS: | ||||
| Yes (n = 173) | 38% | 37% | ||
| E5 (1st phase III study; Greenman et al. 1991) [30] | Severe sepsis (468) | All Patients | 41% | 40% |
| Primary: | ||||
| Gram-negative sepsis | 41% (62/152) | 38% (62/164) | ||
| G-ram-negative sepsis by shock status: | ||||
| No (n = 137) | 43% | 30% | ||
| Yes (n = 179) | 40% | 45% | ||
| E5 (2nd phase III study; Bone et al. 1995) [52] | Severe sepsis (530) | Primary | 26% (69/266) | 30% (79/264) |
| Organ dysfunctions at baseline: | ||||
| 0 (391) | 18% (36/196) | 26% (51/195) | ||
| ≥1 (139) | 47% (33/70) | 41% (28/69) | ||
| E5 (3rd phase III study; Angus et al. 2000) [45] | Severe sepsis (1,090) | Primary | 40% (219/544) | 38% (210/546) |
| Shock: | ||||
| Yes | 46% (145/317) | 46% (140/304) | ||
| No | 33% (74/227) | 29% (70/242) | ||
| Hypotension: | ||||
| Yes | 43% (176/409) | 43% (168/393) | ||
| No | 32% (43/135) | 28% (70/242) | ||
| Lenercept (Abraham et al. 2001) [33] | Severe sepsis (1,342) | Primary | 28% (190/680) | 27% (178/662) |
| SAPS II risk quartile: | ||||
| 0–18% | 13% (23/178) | 15% (25/164) | ||
| 19–31% | 19% (34/178) | 25% (39/155) | ||
| 32–45% | 33% (53/160) | 25% (43/172) | ||
| >45% | 51% (84/164) | 42% (72/171) | ||
| Hypotension: | ||||
| Yes | 32% (36/111) | 42% (47/111) | ||
| No | 28% (159/569) | 24% (132/551) | ||
| Organ dysfunctions at baseline: | ||||
| 0 | 18% (30/164) | 20% (33/164) | ||
| 1 | 25% (78/319) | 23% (71/310) | ||
| 2 | 37% (54/145) | 33% (44/134) | ||
| ≥3 | 52% (27/52) | 56% (30/54) | ||
| ARDS: | ||||
| Yes | 35% (35/101) | 30% (31/104) | ||
| MAK 195F (Reinhart et al. 2001) [46] | Septic shock (446) (IL-6 level > 1,000 pg/ml) | Primary | 58% (128/222) | 54% (121/224) |
| BAYx1351 (1st phase III study) 7.5 mg/kg (Cohen and Carlet 1996) [47] | Severe sepsis (648) | Low Dose | 33% (108/326) | 30% (95/322) |
| Shock: | ||||
| Yes | 46% (76/160) | 38% (59/156) | ||
| No | 21% (35/166) | 22% (36/166) | ||
| BAYx1351 (1st phase III study) 15 mg/kg (Cohen and Carlet 1996) [47] | Severe sepsis (649) | High dose | 33% (108/326) | 31% (101/323) |
| Shock: | ||||
| Yes | 46% (76/160) | 38% (61/162) | ||
| No | 21% (35/166) | 25% (40/161) | ||
| BAYx1351 (2nd phase III study) 3 mg/kg (Abraham et al. 1995) [31] | Severe sepsis (348) | Low dose | 40% (66/167) | 31% (57/181) |
| Shock: | ||||
| Yes | 43% (57/133) | 37% (51/139) | ||
| No | 26% (9/34) | 14% (6/42) | ||
| Shock patients by APACHE II score: | ||||
| ≤24 | 35% (25/72) | 22% (18/82) | ||
| >24 | 53% (31/59) | 57% (32/56) | ||
| BAYx1351 (2nd phase III study) 15 mg/kg (Abraham et al. 1995) [31] | Severe sepsis (372) | High dose | 40% (66/167) | 42% (87/205) |
| Shock: | ||||
| Yes | 43% (57/133) | 45% (66/148) | ||
| No | 26% (9/34) | 37%% (21/57) | ||
| Shock patients by APACHE II score: | ||||
| ≤24 | 35% (25/72) | 36% (30/84) | ||
| >24 | 53% (31/59) | 56% (36/64) | ||
| BAYx1351 (3rd phase III study; (Abraham et al. 1998) [36] | Septic shock (1,869) | Primary | 43% (398/930) | 40% (382/948) |
| IL-6 concentration: | ||||
| ≤1,000 pg/ml | 36% (134/369) | 33% (113/341) | ||
| >1,000 pg/ml | 47% (264/561) | 44% (269/607) | ||
| rhAPC (Bernard et al. 2001 [26]; Ely et al. 2003 [24]) | Severe sepsis (1,960) | Primary | 31% (259/840) | 25% (210/850) |
| Organ dysfunctions at baseline: | ||||
| 1 | 21% (43/203) | 20% (42/215) | ||
| 2 | 26% (71/273) | 21% (56/270) | ||
| 3 | 34% (75/218) | 26% (56/214) | ||
| 4 | 47% (54/116) | 39% (46/119) | ||
| 5 | 53% (16/30) | 32% (10/31) | ||
| IL-6 concentration quartile (low to high): | ||||
| 1st | 22% (48/217) | 11% (20/191) | ||
| 2nd | 27% (50/189) | 26% (58/220) | ||
| 3rd | 33% (67/202) | 29% (59/207) | ||
| 4th | 44% (87/200) | 31% (65/209) | ||
| APACHE II score quartile: | ||||
| 3–19 | 12% (26/215) | 15% (33/218) | ||
| 20–24 | 26% (57/222) | 23% (49/218) | ||
| 25–29 | 36% (58/162) | 24% (48/204) | ||
| 30–55 | 49% (118/241) | 38% (80/210) | ||
| Protrombin time: | ||||
| <14.5 s (n = 103) | 28% | 16% | ||
| 14.5–17.4 s (n = 1,039) | 26% | 17% | ||
| >17.4 s (n = 81) | 51% | 39% | ||
| PAFra (Dhainaut et al. 1998) [48] | Severe sepsis (608) | Primary | 49% (153/308) | 47% (140/300) |
| MAB-T88 (Albertson et al. 2003) [49] | Severe sepsis (826) | All patients | 34% (141/415) | 37% (152/411) |
| Primary: | ||||
| Enterobacteriaceae infection | 31% (70/227) | 34% 978/229) | ||
| NOS inhibitor (Lopez et al. 2004) [50] | Severe sepsis (797) | All Patients | 49% (174/358) | 59% (259/439) |
| HA-1A (Ziegler et al. 1991) [25] | Severe sepsis (200) | All patients | 43% (118/276) | 39% (100/255) |
| Primary: | ||||
| Gram-negative bacteremia | 49% (45/92) | 30% (32/105) | ||
| APACHE II score: | ||||
| ≤25 | 38% (20/52) | 20% (12/62) | ||
| >25 | 60% (26/43) | 48% (21/43) | ||
| Shock: | ||||
| No | 40% (18/45) | 27% (14/51) | ||
| Yes | 57% (27/47) | 33% (18/54) | ||
| Afelimomab (Panacek et al. 2004) [37] | Severe sepsis (2,634) | All patients | 36% (477/1,329) | 32% (421/1,305) |
| Primary: | ||||
| IL-6 level > 1,000 pg/ml | 48% (243/510) | 44% (213/488) | ||
| IL-6 level < 1,000 pg/ml | 29% (234/819) | 25% (208/817) | ||
| Filgrastim (Root et al. 2003) [51] | Pneumonia + severe sepsis (701) | All Patients | 25% (90/353) | 29% (101/348) |
APACHE, Acute Physiology and Chronic Health Evaluation; ARDS, acute respiratory distress syndrome; ATIII, antithrombin III; IL-1ra, IL-1 receptor antagonist; INR, international normalized ratio; NOS, nitric oxide synthase; PAF, platelet activating factor; PAFra, platelet activating factor receptor antagonist; rhAPC, recombinant human activated protein C; SAPS, Simplified Acute Physiology Score; TFPI, tissue factor pathway inhibitor.