TABLE 2.
Primary and Secondary Efficacy Outcomes (Intention-to-Treat Population)
| Outcome | Ruxolitinib 15 mg BID (n = 77) | Ruxolitinib 5 mg BID (n = 87) | Placebo (n = 47) | ||
|---|---|---|---|---|---|
| Primary outcome | |||||
| 28-d mortality | |||||
| Death due to any cause prior to or on Day 29, n/N (%) | 39/77 (51) | 45/85a (53) | 33/47 (70) | ||
| 95% CI for 28-d mortality rate | 39.0–62.2 | 41.8–63.9 | 55.1–82.7 | ||
| Odds ratio (95% CI) for ruxolitinib vs placebo | 0.46 (0.201–1.028) | 0.42 (0.171–1.203) | NA | ||
| One-sided p | 0.029 | 0.028 | NA | ||
| Secondary outcomes | |||||
| In-hospital outcomes | Mean (sd) | P b | Mean (sd) | P b | Mean (sd) |
| Ventilator-free days | 6.3 (9.0) | 0.015 | 4.9 (8.4) | 0.131 | 3.0 (7.2) |
| ICU-free days | 4.8 (7.7) | 0.017 | 4.0 (7.5) | 0.107 | 2.5 (6.4) |
| Vasopressor-free days | 9.0 (11.7) | 0.014 | 7.5 (10.9) | 0.051 | 4.5 (9.3) |
| Hospital-free days | 2.1 (4.9) | 0.190 | 2.4 (5.3) | 0.155 | 1.4 (4.0) |
| Oxygen-free days | 2.7 (6.1) | 0.201 | 3.0 (6.7) | 0.212 | 1.5 (4.7) |
| COVID-19 nine-point ordinal scale score | |||||
| Time to any improvement, median (95% CI) | 9.0 (7.0–14.0) | 13.0 (8.0–19.0) | 11.0 (8.0–not evaluable) | ||
| Day 15, n (%) | |||||
| 0–2 (uninfected/ambulatory) | 4 (5) | 5 (6) | 2 (4) | ||
| 3–5 (hospitalized, not intubated) | 18 (23) | 13 (15) | 3 (6) | ||
| 6–7 (intubated) | 31 (40) | 42 (48) | 13 (28) | ||
| 8 (dead) | 24 (31) | 25 (29) | 29 (62) | ||
| ≥ 1-point improvement from baseline, n/N (%) | 32/77 (42) | 28/85 (33) | 10/47 (21) | ||
| Odds ratio (95% CI) for ruxolitinib vs placebo | 2.54 (1.067–6.034) | 1.72 (0.732–4.041) | NA | ||
| P c | 0.0351 | 0.213 | NA | ||
| ≥ 2-point improvement from baseline, n/N (%) | 17/77 (22) | 13/85 (15) | 5/47 (11) | ||
| Odds ratio (95% CI) for ruxolitinib vs placebo | 2.15 (0.724–6.358) | 1.32 (0.431–4.036) | NA | ||
| P c | 0.169 | 0.628 | NA | ||
| Change from day 1 to day 15, mean (sd) | –0.4 (1.8) | –0.2 (1.7) | 0.6 (1.7) | ||
| Day 29, n (%) | |||||
| 0–2 (uninfected/ambulatory) | 15 (19) | 18 (21) | 6 (13) | ||
| 3–5 (hospitalized, not intubated) | 10 (13) | 6 (7) | 2 (4) | ||
| 6–7 (intubated) | 10 (13) | 14 (16) | 6 (13) | ||
| 8 (dead) | 39 (51) | 45 (52) | 33 (70) | ||
| ≥ 1-point improvement from baseline, n/N (%) | 32/74 (43) | 27/83 (33) | 8/47 (17) | ||
| Odds ratio (95% CI) for ruxolitinib vs placebo | 3.48 (1.406–8.624) | 2.28 (0.899–5.789) | NA | ||
| P c | 0.0070 | 0.0824 | NA | ||
| ≥ 2-point improvement from baseline, n/N (%) | 22/74 (30) | 21/83 (25) | 8/47 (17) | ||
| Odds ratio (95% CI) for ruxolitinib vs placebo | 1.89 (0.751–4.759) | 1.58 (0.616–4.035) | NA | ||
| P c | 0.177 | 0.342 | NA | ||
| Change from day 1 to day 29, mean (sd) | –0.5 (2.5) | –0.4 (2.6) | 0.4 (2.2) | ||
BID = twice a day, NA = not applicable.
aTwo patients in the ruxolitinib 5 mg BID group were not evaluable for analysis of the primary endpoint (withdrawn consent).
b
Per Kruskal-Wallis test; tested (vs placebo) at the 0.05 level using a two-sided test with no type 1 error allocated.
c
Per Wald test from a logistic regression model that included treatment group and acute respiratory distress syndrome severity as fixed effects and investigational site as a random effect; tested (vs placebo) at the 0.05 level using a two-sided test with no type 1 error allocated.