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Table 2 28-Day all-cause mortality by study and by selected subgroups

From: Lack of evidence for qualitative treatment by disease severity interactions in clinical studies of severe sepsis

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)
  1. 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.