Table 4.
Serious and nonserious adverse events captured during the ESCAPE trial
| Anakinra (n = 60) | Tocilizumab (n = 42) | p value | |
|---|---|---|---|
| Serious adverse events, n (%) | |||
| Pneumothorax | 2 (3.3) | 6 (14.3) | 0.06 |
| Pulmonary embolism | 1 (1.7) | 0 (0) | 1.00 |
| Deep venous thrombosis | 1 (1.7) | 0 (0) | 1.00 |
| Acute kidney injury | 7 (11.7) | 5 (11.9) | 1.00 |
| Shock | 17 (28.3) | 10 (23.8) | 0.66 |
| Infections | |||
| Ventilator-associated pneumonia* | 9 (15.0) | 15 (35.7) | 0.02 |
| Catheter-related bloodstream infection | 4 (6.7) | 4 (9.5) | 0.71 |
| Bloodstream infection** | 13 (21.7) | 17 (40.5) | 0.049 |
| Clostridioides difficile infection | 3 (5.0) | 1 (2.4) | 0.64 |
| Arrhythmias | |||
| Ventricular tachycardia | 3 (5.0) | 0 (0) | 0.27 |
| Atrial fibrillation | 6 (10.0) | 4 (9.5) | 1.00 |
| Bradycardia | 0 (0) | 4 (9.5) | 0.03 |
| Grade 4 laboratory investigation | 4 (6.7) | 5 (11.9) | 0.57 |
| Thrombocytopenia | 3 (5.0) | 4 (9.5) | 0.44 |
| Increase of aminotransferases | 0 (0) | 3 (7.1) | 0.07 |
| Increase of CPK | 1 (1.7) | 2 (4.8) | 0.57 |
| Nonserious adverse events | |||
| Grade 1/2 thrombocytopenia | 3 (5.0) | 4 (9.5) | 0.44 |
| Grade 1/2 increase of aminotransferases | 5 (8.3) | 14 (33.3) | 0.002 |
| Grade 1/2 increase of creatinine | 6 (10.0) | 8 (19.1) | 0.25 |
| Grade 1/2 increase of glucose | 3 (5.0) | 2 (4.8) | 1.00 |
| Grade 1/2 hyponatremia | 5 (8.3) | 4 (9.5) | 1.00 |
| Grade 1/2 hypokalemia | 1 (1.7) | 5 (11.9) | 0.08 |
| Grade 1/2 hyperkalemia | 5 (8.3) | 4 (9.5) | 1.00 |
| Grade 1/2 increase of CPK | 0 (0) | 3 (7.1) | 0.07 |
Adverse events were graded according to the Common Terminology Criteria for Adverse Events (version 5.0). Adverse events of grade 4 were considered as serious adverse events. CPK, creatinine phosphokinase. *Pathogens of ventilator-associated pneumonia in the anakinra group were: Acinetobacter baumannii (n = 7); Pseudomonas aeruginosa (n = 1); and Aspergillus spp. (n = 1). Pathogens of ventilator-associated pneumonia in the tocilizumab group were A. baumannii (n = 7); P. aeruginosa (n = 3); Klebsiella pneumoniae (n = 1); Enterobacter cloacae (n = 1); Staphylococcus aureus (n = 1); and Stenotrophomonas maltophilia (n = 1) (2 patients of the tocilizumab arm developed ventilator-associated pneumonia by >1 pathogens, whereas no pathogen was identified in 3 cases). **Bloodstream pathogens in the anakinra group were: A. baumannii (n = 5); Enterococcus faecium (n = 3); K. pneumoniae (n = 2); P. aeruginosa (n = 1); Citrobacter freundii (n = 1); Enterobacter cloacae (n = 1); Enterococcus faecalis (n = 1); Candida albicans (n = 1) (2 patients had >1 pathogens). Bloodstream pathogens in the tocilizumab group were A. baumannii (n = 5); K. pneumoniae (n = 4); E. faecalis (n = 2); E. faecium (n = 2); P. aeruginosa (n = 2); Acinetobacter xylosoxidans (n = 1); S. aureus (n = 1); and Staphylococcus hominis (n = 1) (1 patient had >1 pathogen).