Background
Methods
Participants and setting
Study design
Data collection and measurements
Outcomes
Statistics
Results
Patient randomization and demographics
Parameter | AP301 (n = 20) | Placebo (n = 20) |
---|---|---|
Age, years | 47.6 ± 17.4 | 50.2 ± 14.9 |
Gender, male/female | 14 (70)/6 (30) | 12 (60)/8 (40) |
BMI, kg/m2
| 26.1 ± 3.7 | 28.5 ± 5.2 |
SOFA score | 12.5 ± 3.6 | 11.7 ± 3.4 |
Surgical | 15 (75) | 15 (75) |
Medical | 5 (25) | 5 (75) |
GOCA | ||
Gas exchange | ||
PaO2/FiO2 ratio* | ||
201–300 mmHg (mild) | 2 (10) | 3 (15) |
101–200 mmHg (moderate) | 14 (70) | 11 (55) |
≤ 100 mmHg (severe) | 4 (20) | 6 (30) |
PEEP | ||
0–5 cmH2O | 0 (0) | 0 (0) |
6–10 cmH2O | 9 (45) | 11 (55) |
>10 cmH2O | 11 (55) | 9 (45) |
Organ failure | ||
Lung only | 11 (55) | 10 (50) |
Lung + 1 organ | 4 (20) | 7 (35) |
Lung + 2 organs | 4 (20) | 3 (15) |
Lung + 3 organs | 1 (5) | 0 (0) |
Cause | ||
Direct | 12 (60) | 12 (60) |
Indirect | 8 (40) | 8 (40) |
Associated diseases | ||
No coexisting diseases | 12 (60) | 16 (80) |
Coexisting diseases causing death within 5 years | 6 (30) | 4 (20) |
Coexisting diseases causing death within 6 months | 2 (10) | 0 (0) |
Parameter | AP301 (n = 20) | Placebo (n = 20) |
---|---|---|
PaO2/FiO2, mmHg | 147 ± 48 | 150 ± 59 |
Murray LIS | 2.9 ± 0.5 | 2.8 ± 0.5 |
Oxygenation index | 12.8 ± 5.5 | 10.6 ± 5.0 |
Prone positioning | 6 (30) | 5 (25) |
ECMO therapy | 4 (20) | 1 (5) |
EVLWI, mL/kg PBW | 13.6 ± 5.6 | 12.5 ± 5.0 |
Peak ventilator pressure, cmH2O | 26 ± 4 | 25 ± 4 |
Driving pressure, cmH2O | 14 ± 3 | 14 ± 4 |
Mean airway pressure, cmH2O | 17 ± 4 | 15 ± 3 |
PEEP, cmH2O | 12 ± 3 | 11 ± 2 |
VT, mL/kg PBW | 6.7 ± 1.7 | 7.8 ± 1.6 |
Respiratory rate, per min | 18 ± 6 | 18 ± 3 |
PaCO2, mmHg | 46 ± 7 | 44 ± 9 |
pH | 7.37 ± 0.10 | 7.40 ± 0.07 |
SOFA A | SOFA B | |||
---|---|---|---|---|
Parameter | AP301 (n = 8) | Placebo (n = 7) | AP301 (n = 12) | Placebo (n = 13) |
PaO2/FiO2, mmHg | 180 ± 63 | 188 ± 46 | 147 ± 55 | 156 ± 44 |
Murray LIS | 2.5 ± 0.4 | 2.6 ± 0.3 | 3.2 ± 0.3 | 2.9 ± 0.6 |
Oxygenation index | 9.3 ± 4.5 | 7.8 ± 2.2 | 15.1 ± 5.1 | 12.1 ± 5.5 |
Prone positioning | 2 (25) | 0 | 4 (33.3) | 5 (38.5) |
ECMO therapy | 0 | 0 | 4 (33.3) | 1 (7.8) |
EVLWI, mL/kg PBW | 10.2 ± 1.4 | 12.7 ± 4.3 | 15.8 ± 6.2 | 12.5 ± 5.5 |
Peak ventilator pressure, cmH2O | 23 ± 3 | 23 ± 5 | 28 ± 4 | 26 ± 4 |
Driving pressure, cmH2O | 14 ± 3 | 13 ± 5 | 15 ± 3 | 15 ± 4 |
Mean airway pressure, cmH2O | 14 ± 2 | 14 ± 1 | 19 ± 4 | 16 ± 3 |
PEEP, cmH2O | 10 ± 2 | 10 ± 1 | 13 ± 3 | 11 ± 2 |
VT, mL/kg PBW | 7.7 ± 1.3 | 8.0 ± 1.3 | 6.0 ± 1.5 | 7.6 ± 1.7 |
Respiratory rate, per min | 16 ± 2 | 17 ± 2 | 19 ± 7 | 18 ± 4 |
PaCO2, mmHg | 45 ± 5 | 40 ± 3 | 48 ± 7 | 47 ± 10 |
pH | 7.43 ± 0.07 | 7.43 ± 0.03 | 7.33 ± 0.10 | 7.38 ± 0.08 |
Condition | Assignment to groups (n) |
n (%) |
---|---|---|
Multiple trauma | AP301: 2, Placebo: 3 | 5 (12.5) |
Pneumonia | AP301: 3, Placebo: 2 | 5 (12.5) |
Sepsis | AP301: 1, Placebo: 3 | 4 (10) |
Subarachnoidal hemorrhage | AP301: 1, Placebo: 2 | 3 (7.5) |
Respiratory failure following abdominal surgery | AP301: 3 | 3 (7.5) |
Burn injury >40% of body surface | AP301: 3 | 3 (7.5) |
Perforation of the small intestine or colon | AP301: 2, Placebo: 1 | 3 (7.5) |
Traumatic brain injury | Placebo: 2 | 2 (5) |
Cerebral ischemia | AP301: 1, Placebo: 1 | 2 (5) |
Other causes | AP301: 4, Placebo: 6 | 10 (25) |
Primary efficacy variable
Group | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 |
---|---|---|---|---|---|---|---|
AP301 | 0.2 ± 3.1 | 0.7 ± 3.7 | 1.3 ± 4.5 | 2.0 ± 6.3 | 2.7 ± 6.7 | 4.2 ± 5.9 | 4.5 ± 5.6 |
Placebo | –0.5 ± 3.3 | –0.2 ± 3.3 | 0.6 ± 3.1 | 1.2 ± 3.6 | 1.0 ± 4.7 | 1.0 ± 6.1 | 1.9 ± 4.1 |
Stratum A AP301 | –0.7 ± 4.3 | 0.5 ± 3.7 | –0.2 ± 3.4 | –0.6 ± 7.4 | –1.2 ± 7.2 | 0.6 ± 3.9 | 1.3 ± 2.6 |
Stratum A placebo | 0.4 ± 0.5 | 1.0 ± 1.6 | 1.5 ± 2.4 | 1.8 ± 1.9 | –0.5 ± 8.8 | 1.4 ± 4.5 | 2.0 ± 3.8 |
Stratum B AP301 | 0.9 ± 1.7 | 1.0 ± 3.9 | 2.4 ± 5.0 | 4.0 ± 4.9 | 5.5 ± 4.9 | 6.4 ± 6.0 | 6.6 ± 6.1 |
Stratum B placebo | –1.0 ± 4.1 | –0.9 ± 3.8 | 0.1 ± 3.5 | 0.9 ± 4.2 | 1.3 ± 4.3 | 0.8 ± 7.0 | 1.8 ± 4.5 |
Secondary outcome parameters
Screening | Day 7 | |||
---|---|---|---|---|
Parameter | AP301 | Placebo | AP301 | Placebo |
HR, per min | 90 ± 18 | 83 ± 22 | 96 ± 23 | 84 ± 20 |
SBP, mmHg | 112 ± 12 | 121 ± 20 | 121 ± 14 | 133 ± 25 |
CI, L/min/m | 3.8 ± 1.2 | 3.3 ± 0.9 | 3.9 ± 1.2 | 3.7 ± 0.9 |
Noradrenalin dose, mg/24 h | 16.3 (0–86.3) | 9.5 (0–72.1) | 5.6 (0–32.0) | 3.0 (0–25.6) |
PBV, mL | 351 ± 109 | 384 ± 180 | 322 ± 89 | 406 ± 228 |
EVLWI, mL/kg PBW | 13.6 ± 5.6 | 12.5 ± 5.0 | 9.0 ± 2.2 | 11.5 ± 5.1 |
24-h fluid balance, mL | 1307 ± 1525 | 975 ± 1732 | –421 ± 1183 | –467 ± 1102 |
Peak ventilator pressure, cmH2O | 26 ± 4 | 25 ± 4 | 21 ± 7 | 21 ± 7 |
Driving pressure, cmH2O | 14 ± 3 | 14 ± 4 | 9 ± 5 | 10 ± 4 |
PEEP, cmH2O | 12 ± 3 | 11 ± 2 | 10 ± 4 | 10 ± 2 |
PaO2/FiO2, mmHg | 147 ± 48 | 150 ± 59 | 211 ± 60 | 192 ± 60 |
Murray LIS | 2.9 ± 0.5 | 2.8 ± 0.5 | 2.0 ± 0.7 | 2.1 ± 0.6 |
Prone positioning | 6 (30) | 5 (25) | 2 (10) | 3 (15) |
ECMO therapy | 4 (20) | 1 (5) | 0 | 1 (5) |
Additional analyses
Adverse events
Adverse event | AP301 (n = 20) | Placebo (n = 20) | Total (n = 40) |
---|---|---|---|
Tracheostomy | 5 (25) | 8 (40) | 13 (32.5) |
Anemia | 3 (15) | 6 (30) | 9 (22.5) |
Worsening of existing anemia | 5 (25) | 2 (10) | 7 (17.5) |
Cardiac arrest | 5 (25) | 1 (5) | 6 (15) |
Fever | 1 (5) | 4 (20) | 5 (12.5) |
Thrombopenia | 3 (15) | 1 (5) | 4 (10) |
Leucocytosis | 3 (15) | 1 (5) | 4 (10) |
Atrial flutter/fibrillation | 1 (5) | 3 (15) | 4 (10) |
Pleural effusion | 0 (0) | 3 (15) | 3 (7.5) |