Table 2.
Primary and secondary endpoints
| Alteplase pooled N = 69 |
SOC alone N = 35 |
p-value | |
|---|---|---|---|
| Primary endpoint | |||
| Time to clinical improvement* up to Day 28 | |||
| Median days to clinical improvement (95% CI) | 25 (17 to NR) | NR† | |
| Patients with event, n (%) | 37 (54) | 15 (43) | |
| HR vs. SOC (95% CI) | |||
| Unadjusted | 1.31 (0.72 to 2.38) | – | 0.383 |
| Adjusted‡ | 1.23 (0.67 to 2.27) | – | 0.502 |
| Risk difference vs. SOC (95% CI) | 11% (− 9 to 31) | ||
| Key secondary endpoints | |||
| Treatment failure (all-cause mortality or mechanical ventilation) up to Day 28 | |||
| Patients with event, n (%) | 27 (39) | 17 (49) | |
| Risk difference vs. SOC (95% CI) | |||
| Unadjusted | − 9% (− 30 to 11) | – | 0.359 |
| Adjusted‡ | − 8% (− 27 to 12) | – | 0.448 |
| All-cause mortality up to Day 28 | |||
| Patients with event, n (%) | 8 (12) | 10 (29) | |
| HR vs. SOC (95% CI) | |||
| Unadjusted | 0.39 (0.15 to 0.99) | – | 0.048 |
| Adjusted‡ | 0.42 (0.16 to 1.10) | – | 0.077 |
| Risk difference vs. SOC (95% CI) | |||
| Unadjusted | − 17% (− 34 to 0) | – | 0.047 |
| Adjusted‡ | − 16% (− 31 to 1) | – | 0.058 |
| Other secondary endpoints | |||
| PaO2/FiO2 ratio (worst daily value) change from baseline up to Day 6 | |||
| Mean ± SD, mmHg | 30.3 ± 84.3 | − 11.7 ± 59.1 | |
| Mean difference vs. SOC (95% CI) | |||
| Unadjusted | 37 (5 to 69) | – | 0.023 |
| Adjusted§ | 30 (0 to 59) | – | 0.052 |
| Length of hospital stay up to Day 28¶ | |||
| Mean ± SD, days | 23.0 ± 7.3 | 24.4 ± 5.9 | |
| Mean difference vs. SOC (95% CI) | |||
| Unadjusted | − 1.4 (− 4 to 1) | – | 0.331 |
| Adjusted‡ | − 1.0 (− 4 to 2) | – | 0.449 |
| Number of oxygen-free days up to Day 28¶ | |||
| Mean ± SD, days | 6.7 ± 8.4 | 4.5 ± 7.1 | |
| Mean difference vs. SOC (95% CI) | |||
| Unadjusted | 2.2 (− 1 to 6) | – | 0.188 |
| Adjusted‡ | 1.7 (− 2 to 5) | – | 0.291 |
| Further endpoint | |||
| All-cause mortality up to Day 90 | |||
| Patients with event, n (%) | 17 (25) | 14 (40) | |
| Risk difference vs. SOC (95% CI) | |||
| Unadjusted | − 15% (− 35 to 4) | – | 0.116 |
| Adjusted‡ | − 14% (− 33 to 4) | – | 0.134 |
| Safety endpoint | |||
| Major bleeding event up to Day 6 | |||
| Patients with event, n (%) | 9 (13) | 0 (0) | |
| Risk difference vs. SOC (95% CI) | 13% (1 to 23) | – | < 0.05 |
Alteplase pooled: 0.3 or 0.6 mg/kg over 2 h, followed by daily long-term (12-h) infusion of 0.02 or 0.04 mg/kg/h over 5 days (added to SOC)
CI confidence interval, FiO2 fraction of inspired oxygen, HR hazard ratio, NA not available, NR not reached, PaO2 partial pressure of oxygen, SD standard deviation, SOC standard of care, WHO World Health Organization
*Improvement of ≥2 points on the 11-point WHO Clinical Progression Scale, or discharge from the hospital, whichever came first
†WHO Clinical Progression score was recorded up to 28 days, and by Day 28, less than 50% of SOC patients had a clinical improvement. Therefore, median (50%) was not reached by Day 28
‡Adjusted for treatment, baseline D-dimer status, age, baseline ventilation status, and Part 1 or 2 of the study
§Adjusted for treatment, baseline PaO2/FiO2 ratio, baseline D-dimer status, age, baseline ventilation status, and Part 1 or 2 of the study
¶In the event of death, the length of a patient’s hospital stay was automatically recorded as 28 days, and the number of oxygen-free days was 0