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Table 1 Overview of key recent critical care sepsis trials

From: Designing phase 3 sepsis trials: application of learned experiences from critical care trials in acute heart failure

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)
  1. ICU intensive care unit, MAP mean arterial pressure, EGDT early goal-directed therapy, SIRS systemic inflammatory response syndrome, CXR chest radiography, Hgb hemoglobin, ED emergency department
  2. aIncludes subscores ranging from 0 to 4 for each of five components (respiratory, coagulation, liver, cardiovascular, and renal components), with higher scores indicating more severe organ dysfunction. The scoring was modified by excluding the assessment of cerebral failure (the Glasgow Coma Scale), which was not performed in these patients, and by decreasing to 65 mmHg the mean arterial pressure threshold for a cardiovascular subscore of 1, for consistency with the hemodynamic targets as defined according to the early goal-directed therapy
  3. bIncludes subscores ranging from 0 to 4 for each of five components (circulation, lungs, liver, kidneys, and coagulation). Aggregated scores range from 0 to 20, with higher scores indicating more severe organ failure
  4. cSubscores ranging from 0 to 4 for each of six organ systems (cerebral, circulation, pulmonary, hepatic, renal, and coagulation). The aggregated score ranges from 0 to 24, with higher scores indicating more severe organ failure. One variable was missing for 51 patients in the higher-threshold group and for 64 in the lower-threshold group, so their values were not included
  5. dScores range from 0 to 24, with higher scores indicating a greater degree of organ failure. The SOFA score was calculated on the basis of the last recorded data before randomization. The SOFA renal score was based on the plasma creatinine level only and did not include urine output
  6. e ARDS acute respiratory distress syndrome
  7. f SOFA sequential organ failure assessment