TABLE 2.
Safety and Efficacy Endpoints
| Intention-to-Treat Population | EA-230 (n = 91) | Placebo (n = 89) | p |
|---|---|---|---|
| Safety | |||
| TE adverse events, number of events (n [%]) | 217 (n = 78 [86]) | 218 (n = 81 [91]) | — |
| TE serious adverse events, number of events (n [%]) | 13 (n = 12 [13]) | 19 (n = 17 [19]) | — |
| Suspected unexpected serious adverse reactions, number of events (n [%]) | 0 (n = 0 [0]) | 1 (n = 1 [1]) | — |
| Major clinical adverse event related to cardiac surgery, number of events (n [%]) | 11 (n = 11 [12]) | 15 (n = 15 [17]) | — |
| Per-Protocol Population | EA-230 (n = 90) | Placebo (n = 89) | |
| Efficacy—inflammatory | |||
| Interleukin-6 (peak in pg/mL) | 189 [141–293] | 213 [154–287] | 0.99a |
| Leukocyte numbers (peak in ×109/L) | 13 [11–16] | 13 [10–16] | 0.25a |
| Body temperature (peak in °C) | 37.1 ± 0.06 | 37.4 ± 0.06 | 0.08a |
| Insulin dose (total units during the first 24 hr of ICU admission) | 3.3 [0–25] | 0 [0–26] | 0.77a |
| Glucose (peak in mmol/L) | 9.0 ± 0.16 | 9.1 ± 0.16 | 0.58a |
| Efficacy—renal | |||
| GFR using plasma clearance of iohexol (change from day before surgery to POM in mL/min/1.73 m2) | 19 ± 1.2 | 16 ± 2 | 0.13a |
| GFRMDRD (change from day before surgery to POM in mL/min/1.73 m2) | 6 ± 1 | 2 ± 1 | 0.01a |
| Occurrence rate of acute kidney injury, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria stage “injury” | 6 (7) | 16 (18) | 0.07b |
| Plasma creatinine (change from day before surgery to POM in µmol/L) | –5.6 ± 1.1 | 1.1 ± 1.9 | 0.003a |
| Plasma creatinine (peak during POD 1–7 in µmol/L) | 82 ± 5 | 96 ± 11 | 0.02a |
| GFRMDRD (lowest during POD 1–7 in mL/min/1.73 m2) | 86 ± 5 | 80 ± 5 | 0.66a |
| GFR to calculate endogenous creatinine clearance (change from day before surgery to POM in mL/min/1.73 m2) | 106 ± 4 | 104 ± 5 | 0.70a |
| Urine output (total mL during the first 24 hr in ICU) | 1,815 [1,439–2,123] | 1,685[1,433–2,080] | 0.30a |
| Urinary creatinine (nadir in mmol/L) | 4.1 [3.2–5.7] | 3.7 [2.6–5.5] | 0.03a |
| Urinary urea (peak in mmol/L) | 150 [112–189] | 111 [81–144] | 0.004a |
| Efficacy—cardiovascular | |||
| Net fluid balance (total mL during the first 24 hr of ICU admission) | 787 ± 109 | 1,080 ± 117 | 0.98a |
| Fluid therapy (total mL during the first 24 hr of ICU admission) | 3,272[2,762–6,174] | 3,423[3,023–3,986] | 0.84a |
| Drain production (total mL during the first 24 hr of ICU admission) | 704 [558–913] | 765 [578–932] | 0.79a |
| Alveolar-arterial gradient (change from ICU admission to POM) | –9.7 ± 1.2 | –8.6 ± 1.4 | 0.78a |
| Efficacy—general | |||
| Length of stay in ICU (in hr) | 21 [19–23] | 22 [19–24] | 0.02c |
| Length of stay in hospital (in hr) | 195 [171–265] | 234 [192–295] | 0.001c |
| Sequential Organ Failure Assessment (change in score from ICU admission to POM) | –1 [–2 to 1] | –1 [–2.5 to 0] | 0.35a |
| Acute Physiology and Chronic Health Evaluation IV (score at ICU admission) | 53 ± 2 | 56 ± 2 | 0.26d |
GFR = glomerular filtration rate, GFRMDRD = glomerular filtration rate with the Modification of Diet in Renal Disease, POD = postoperative day, POM = postoperative morning, TE = treatment-emergent.
ap values calculated using repeated measures two-way analysis of variance (interaction term) on plasma concentration-time effect curves (depicted in supplemental material, http://links.lww.com/CCM/G114).
b p values calculated using Pearson chi-squared test.
cp values calculated using log-rank test.
dp values calculated using Mann-Whitney U tests or Student t tests, depending on the distribution of the data.
No statistical testing was performed on safety data. In Table S2 (http://links.lww.com/CCM/G114), safety data categorized on severity and organ class is reported.
Data are presented as mean ± sem or median [interquartile range] or frequency (percentage).