Table 2.
Primary and secondary outcomes
| Outcomes | Terlipressin (n = 66) |
Placebo (n = 64) |
Relative risk (95%CI) | P |
|---|---|---|---|---|
| Primary outcomes | ||||
| Achieve target MAP ≥ 65 mmHg with norepinephrine and/or epinephrine dose ≤ 0.2 mcg/kg/min at 6th h, n (%) | 15 (22.7) | 6 (9.4) | 1.53 (1.09–2.14) | 0.039 |
| Secondary outcomes | ||||
| Hospital mortality, n (%) | 45 (68.2) | 48 (75.0) | 0.85 (0.60–1.21) | 0.389 |
| 28-d mortality, n (%) | 40 (60.6) | 41 (64.1) | 0.93 (0.66–1.31) | 0.684 |
| ICU mortality, n (%) | 39 (59.1) | 37 (57.8) | 1.03 (0.73–1.45) | 0.882 |
| Achieve target MAP ≥ 65 mmHg with norepinephrine and/or epinephrine dose ≤ 0.2 mcg/kg/min at 24th h, n (%) | 27 (40.9) | 19 (29.7) | 1.26 (0.91–1.77) | 0.181 |
| Achieve target MAP ≥ 65 mmHg with no vasopressor at 72nd h, n (%) | 32 (48.9) | 26 (40.6) | 1.17 (0.83–1.64) | 0.306 |
| Time to achieve MAP ≥ 65 mmHg, median (IQR), h:min | 1 (0:00–1:30) | 1 (0:15–2:00) | 0.437 | |
| Serum lactate decrease at 6 h, %a | −11 (−35 to 16) | −5 (−35 to 18) | 0.762 | |
| Catecholamine duration, median (IQR), h | 61 (37–88) | 67 (38–111) | 0.463 | |
| Study drug duration, median (IQR), h | 24 (13–46) | 28 (9–48) | 0.903 | |
| Vasoactive dose (include terlipressin) at 24 h, median (IQR), mcg/kg/minb | 0.16 (0.04–0.42) | 0.26 (0.09–0.43) | 0.084 | |
| Catecholamine dose (did not include terlipressin) at 24 h, median (IQR), mcg/kg/minc | 0.15 (0.04–0.41) | 0.26 (0.09–0.43) | 0.037 | |
| Maximum terlipressin dose, median (IQR), mcg/kg/mind | 0.007 (0.005–0.019) | 0.008 (0.005–0.026) | 0.684 | |
|
Days alive and free of vasopressors to Day 28, median (IQR), d |
||||
| -Overall patients | 1 (0–20) | 5 (0–22) | 0.667 | |
| -Survival patientse | 22 (16–24) | 22 (8–25) | 0.976 | |
| Mechanical ventilation, n (%) | 59 (89.4) | 60 (93.8) | 0.72 (0.32–1.61) | 0.372 |
|
Days alive and free of mechanical ventilator to Day 28, median (IQR), d |
||||
| -Overall patients | 0 (0–6) | 0 (0–11) | 0.453 | |
| -Survival patientse | 9 (1–22) | 12 (8–24) | 0.129 | |
| Renal replacement therapy, n (%) | 42 (63.6) | 44 (68.8) | 0.89 (0.61–1.30) | 0.410 |
|
Days alive and free of renal replacement therapy to Day 28, median (IQR), d |
||||
| -Overall patients | 1 (0–21) | 3 (0–24) | 0.385 | |
| -Survival patientse | 24 (12–28) | 21 (12–28) | 0.992 | |
|
Days alive and free of organ support to Day 28, median (IQR), d |
||||
| -Overall patients | 0 (0–6) | 0 (0–8) | 0.191 | |
| -Survival patientse | 8 (0–21) | 12 (4–24) | 0.173 | |
| LVEF at 24th h, median (IQR), (%) | 50 (44–63) | 50 (40–66) | 0.459 | |
| Cardiac index at 24th h, median (IQR), L/min/m2 | 3.4 (2.7–4.5) | 2.8 (2.0–3.8) | 0.886 | |
| ICU length of stay, median (IQR), d | 8 (4–15) | 7 (4–18) | 0.777 | |
| Hospital length of stay, median (IQR), d | 15 (5–30) | 20 (6–31) | 0.526 | |
| Adverse events, n (%) | ||||
| Arrhythmia | ||||
| - Atrial fibrillation | 9 (13.6) | 8 (12.5) | 1.05 (0.61–1.80) | 0.848 |
| - Supraventricular tachycardia | 4 (6.1) | 3 (4.7) | 1.16 (0.48–2.77) | 1.000 |
| -Ventricular fibrillation/tachycardia | 3 (4.5) | 3 (4.7) | 0.98 (0.43–2.23) | 1.000 |
| Digital ischemia | 19 (28.8) | 17 (27.4) | 1.04 (0.69–1.55) | 0.863 |
| Digital gangrene | 2 (3.0) | 1 (1.6) | 1.48 (0.29–7.44) | 1.000 |
| Bowel ischemia | 0 (0) | 2 (3.1) | 0.48 (0.41–0.58) | 0.240 |
| Recurrent shock | 23 (34.8) | 21 (32.8) | 1.05 (0.72–1.52) | 0.806 |
Abbreviations: MAP mean arterial pressure, LVEF left ventricular ejection fraction, mcg/kg/min micrograms per kilogram per minute, d days, h hours, ICU intensive care unit, IQR interquartile range, L/min liters per minute, L/min/m2 liters per minute per square meter, mmol/L millimoles per liter
aThe decrease in the serum lactate concentration (%) was calculated with the following equation:
([serum lactate at baseline – serum lactate at 6 h after start study drug]/serum lactate at baseline) × 100. The negative value indicated decreasing of lactate from baseline, while positive value indicated increasing of lactate from baseline
bVasoactive dose or norepinephrine dose equivalents (included terlipressin dose) were calculated with the following equation:
Norepinephrine dose equivalent (micrograms per kilogram per minute [mcg/kg/min]) = (norepinephrine [mcg/kg/min] + epinephrine [mcg/kg/min] + dopamine [mcg/kg/min]/100 + 10 × terlipressin dose [mcg/kg/min]) [25].
cCatecholamine dose (did not include terlipressin dose) were calculated with the following equation:
Norepinephrine dose equivalent (micrograms per kilogram per minute [mcg/kg/min]) = (norepinephrine [mcg/kg/min] + epinephrine [mcg/kg/min] + dopamine [mcg/kg/min]/100) [18].
dFor the placebo group, the actual terlipressin dose was zero. The illustrated dose represents an estimated value, calculated based on the placebo infusion rate and the patient's body weight
eData analyzed from 26 patients in terlipressin group and 23 patients in placebo group who survived to day 28