Trial | Design | Intervention | Study population | Mean SOFAf score | Endpoint | Length of follow-up | N of deaths | Primary endpoint results |
---|---|---|---|---|---|---|---|---|
ALBIOS [22] | Multicenter, open-label, randomized, controlled | 20 % albumin + crystalloid vs. crystalloid alone for 28 days or until ICU discharge | N = 1818 ≥18 years, clinical criteria for severe sepsis [76] | Albumin 8 (6–10) vs. crystalloid 8 (5–10)a, median (interquartile range) | All-cause mortality | 28 days | 285 albumin vs. 288 crystalloid | 31.8 % albumin vs. 32 % crystalloid (RR 1.00, 95 % CI 0.87–1.14, P = 0.94) |
SEPSISPAM [21] | Multicenter, open-label, randomized | Vasopressor treatment adjusted to maintain MAP of 80–85 mmHg (high target) vs. 65–70 mmHg (low target) for 5 days or until vasopressor support weaned | N = 776 Septic shock (Table 2) refractory to fluid resuscitation, requiring vasopressors | Low target 10.8 ± 3.1 vs. high target 10.7 ± 3.1b | All-cause mortality | 28 days | 142 high target vs. 132 low target | 36.6 % high target vs. 34 % low target (HR for high target 1.07, 95 % CI 0.84–1.38, P = 0.57) |
ProCESS [26] | Multicenter, randomized | Protocol-based EGDT vs. protocol-based standard therapy vs. usual care | N = 1341 Suspected sepsis with ≥2 criteria for SIRS, [76] and refractory hypotension or serum lactate ≥4 mmol/L | Not reported | All-cause in-hospital death | 60 days | 92 EGDT vs. 81 standard therapy vs. 86 usual care | 21 % EGDT vs. 18.2 % standard therapy vs. 18.9 % usual care Combined protocol-based groups vs. usual care RR 1.04, 95 % CI 0.82–1.31, P = 0.83 |
Rosuvastatin for ARDSe [25] | Multicenter, randomized, placebo-controlled, double-blind | Enteral rosuvastatin vs. placebo | N = 745 Positive pressure mechanical ventilation, PaO2 to FIO2 ratio ≤300, bilateral infiltrates on CXR without evidence of left atrial hypertension, known or suspected infection, and ≥1 criteria for SIRS (Table 2) | Not reported | All-cause mortality before hospital discharge home or until study day 60 | 60 days | 108 rosuvastatin vs. 91 placebo | 28.5 % rosuvastatin vs. 24.9 % placebo; difference 4.0 (−2.3 to 10.2), P = 0.21; enrollment stopped prematurely for futility |
TRISS [23] | Multicenter, randomized, parallel-group | Leuko-reduced blood transfusion at lower (≤7 g/dL) vs. higher (≤9 g/dL) Hgb thresholds | N = 1000 ICU, fulfilled septic shock criteria (Table 2), Hgb ≤9 g/dL | Both groups 10 (8-12)c, median (interquartile range) | All-cause mortality | 90 days | 216 lower Hgb vs. 223 higher Hgb | 43 % lower threshold vs. 45 % higher threshold (RR 0.94, 95 % CI 0.78 to 1.09, P = 0.44) |
ARISE [24] | Multicenter, randomized, parallel-group | EGDT vs. usual care for 6 h | N = 1600 Suspected or confirmed infection, ≥2 criteria for SIRS (Table 2), refractory hypotension or hypoperfusion, identified in the ED within 6 h of presentation | Not reported | All-cause mortality | 90 days | 147 EGDT vs. 150 usual care | 18.6 % EGDT vs. 18.8 % usual care (RR 0.98, 95 % CI 0.80 to 1.21, P = 0.9) |
PROMISE [31] | Pragmatic, open, multicenter, parallel-group, randomized, controlled trial | 6-h EGDT resuscitation protocol vs. usual care | N = 1260 Known or presumed infection, ≥2 SIRS criteria, and either refractory hypotension or hyperlactatemia within 6 h after ED presentation | EGDT 4.2 ± 2.4 vs. usual care 4.3 ± 2.4d | All-cause mortality | 90 days | 184 EGDT vs. 181 usual care | 29.5 % EGDT vs. 29.2 % usual care (RR 1.01, 95 % CI 0.85 to 1.20, P = 0.9) |