Table 1.
Primary and secondary outcomes for patients included in the DisCoVeRy trial for L/r, L/r plus IFN-β-1a, and HCQ, according to disease severity at baseline
| Overall (N = 593) |
Control (n = 149) |
L/r (n = 147) |
L/r + IFN-ß-1a (n = 147) |
HCQ (n = 150) |
L/r vs. control effect measure (95% CI) |
L/r + IFN-ß-1a vs. control effect measure (95% CI) |
HCQ vs. control effect measure (95% CI) |
||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Moderate (n = 379) | Severe (n = 214) | Moderate (n = 95) | Severe (n = 54) | Moderate (n = 95) | Severe (n = 52) | Moderate (n = 93) | Severe (n = 54) | Moderate (n = 96) | Severe (n = 54) | ||||
| 7-point ordinal scale at day 15, n (%) | |||||||||||||
| 1. Not hospitalized, no limitations on activities | 83 (21.9) | 3 (1.4) | 22 (23.2) | 1 (1.9) | 21 (22.1) | 1 (1.9) | 20 (21.5) | 0 (0.0) | 20 (20.8) | 1 (1.9) | OR = 0.82 (0.54 to 1.25) [P = 0.36] | OR = 0.69 (0.45 to 1.05) [P = 0.08] | OR = 0.94 (0.62 to 1.41) [P = 0.76] |
| 2. Not hospitalized, limitation on activities | 155 (40.9) | 16 (7.5) | 44 (46.3) | 6 (11.1) | 37 (38.9) | 2 (3.8) | 37 (39.8) | 1 (1.9) | 37 (38.5) | 7 (13.0) | |||
| 3. Hospitalized, not requiring supplemental oxygen | 53 (14.0%) | 25 (11.7%) | 8 (8.4%) | 5 (9.3%) | 14 (14.7%) | 6 (11.5%) | 13 (14.0%) | 6 (11.1%) | 18 (18.8%) | 8 (14.8%) | |||
| 4. Hospitalized, requiring supplemental oxygen | 40 (10.6) | 32 (15.0) | 10 (10.5) | 10 (18.5) | 10 (10.5) | 9 (17.3) | 9 (9.7) | 6 (11.1) | 11 (11.5) | 7 (13.0) | |||
| 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices | 6 (1.6%) | 8 (3.7%) | 1 (1.1%) | 2 (3.7%) | 2 (2.1%) | 1 (1.9%) | 2 (2.2%) | 3 (5.6%) | 1 (1.0%) | 2 (3.7%) | |||
| 6. Hospitalized, on invasive mechanical ventilation or ECMO | 27 (7.1) | 107 (50.0) | 6 (6.3) | 24 (44.4) | 8 (8.4) | 29 (55.8) | 8 (8.6) | 28 (51.9) | 5 (5.2) | 26 (48.1) | |||
| 7. Death | 15 (4.0) | 23 (10.7) | 4 (4.2) | 6 (11.1) | 3 (3.2) | 4 (7.7) | 4 (4.3) | 10 (18.5) | 4 (4.2) | 3 (5.6) | |||
| 7-point ordinal scale at day 29, n (%) | |||||||||||||
| 1. Not hospitalized, no limitations on activities | 150 (39.6) | 20 (9.3) | 36 (37.9) | 7 (13.0) | 35 (36.8) | 6 (11.5) | 36 (38.7) | 1 (1.9) | 43 (44.8) | 6 (11.1) | OR 0.95 (0.63 to 1.43) (p = 0.80 | OR 0.80 (0.53 to 1.21) (p = 0.29) | OR 1.26 (0.84 to 1.90) (p = 0.27) |
| 2. Not hospitalized, limitation on activities | 135 (35.6) | 34 (15.9) | 35 (36.8) | 5 (9.3) | 39 (41.1) | 8 (15.4) | 31 (33.3) | 9 (16.7) | 30 (31.3) | 12 (22.2) | |||
| 3. Hospitalized, not requiring supplemental oxygen | 40 (10.6) | 47 (22.0) | 11 (11.6) | 15 (27.8) | 9 (9.5) | 8 (15.4) | 10 (10.8) | 11 (20.4) | 10 (10.4) | 13 (24.1) | |||
| 4. Hospitalized, requiring supplemental oxygen | 14 (3.7) | 20 (9.3) | 5 (5.3) | 6 (11.1) | 3 (3.2) | 4 (7.7) | 4 (4.3) | 6 (11.1) | 2 (2.1) | 4 (7.4) | |||
| 5. Hospitalized, on non-invasive ventilation or high flow oxygen devices | 5 (1.3) | 7 (3.3) | 1 (1.1) | 1 (1.9) | 2 (2.1) | 2 (3.8) | 1 (1.1) | 1 (1.9) | 1 (1.0) | 3 (5.6) | |||
| 6. Hospitalized, on invasive mechanical ventilation or ECMO | 14 (3.7) | 50 (23.4) | 2 (2.1) | 12 (22.2) | 3 (3.2) | 14 (26.9) | 5 (5.4) | 13 (24.1) | 4 (4.2) | 11 (20.4) | |||
| 7. Death | 21 (5.5) | 36 (16.8) | 5 (5.3) | 8 (14.8) | 4 (4.2) | 10 (19.2) | 6 (6.5) | 13 (24.1) | 6 (6.3) | 5 (9.3) | |||
| Time to improvement of 2 categories of the 7-point ordinal scale or hospital discharge within day 29, d, median (IQR) | 10 (7–17) | 21 (13–29) | 9 (6–14) | 18 (10–29) | 12 (8–17) | 28 (14–29) | 11 (8–19) | 29 (1629) | 10 (7–19) | 18 (12–29) | HR 0.70 (0.54 to 0.92) (p = 0.01) | HR 0.68 (0.52 to 0.89) (p = 0.008) | HR 0.79 (0.61 to 1.03) (p = 0.09) |
| Time to National Early Warning Score ≤2 or hospital discharge within 29 days, d, median (IQR) | 9 (5–16) | 29 (19–29) | 8 (5–14) | 29 (19–29) | 10 (6–16) | 29 (21–29) | 10 (6–18) | 29 (29–29) | 9 (5–15) | 29 (16–29) | HR 0.84 (0.64 to 1.10) (p = 0.21) |
HR 0.72 (0.54 to 0.96) (p = 0.02) | HR 0.93 (0.71 to 1.23) (p = 0.63) |
| Time to hospital discharge within 29 days, d, median (IQR) | 11 (7–21) | 29 (22–29) | 9 (6–16) | 29 (19–29) | 12 (8–21) | 29 (23–29) | 11 (8–26) | 29 (29–29) | 11 (8–21) | 29 (17–29) | HR 0.81 (0.61 to 1.08) (p = 0.15) |
HR 0.72 (0.54 to 0.97) (p = 0.03) | HR 0.84 (0.63 to 1.12) (p = 0.24) |
| Oxygenation-free days until day 29, d, median (IQR) | 22 (15–25) | 0 (0–13) | 22 (15–25) | 4 (0–14) | 22 (15–25) | 0 (0–13) | 22 (15–25) | 0 (0–7) | 22 (17–25) | 5 (0–15) | LSMD = -0.99 (-2.92 to 0.95) (p = 0.32) |
LSMD = -1.70 (-3.63 to 0.24) (p = 0.09) | LSMD = 0.06 (-1.89 to 2.01) (p = 0.95) |
| Ventilator-free days until day 29, d, median (IQR) | 29 (29–29) | 11 (0–20) | 29 (29–29) | 13 (0–22) | 29 (29–29) | 5 (0–20) | 29 (29–29) | 4 (0–16) | 29 (29–29) | 14 (1–22) | LSMD = -0.75 (-2.72 to 1.22) (p = 0.46) | LSMD = -2.07 (-4.08 to -0.05) (p = 0.05) | LSM D = 0.35 (-1.64 to 2.34) (p = 0.73) |
| In-hospital mortality,n (%) | 20 (5.3) | 36 (16.8) | 5 (5.3) | 8 (14.8) | 4 (4.2) | 10 (19.2) | 5 (5.4) | 13 (24.1) | 6 (6.3) | 5 (9.3) | OR 1.12 (0.50 to 2.51) (p = 0.70) |
OR 1.47 (0.68 to 3.18) (p = 0.32) | OR 0.89 (0.36 to 1.92) (p = 0.66) |
| Death within 28 days,n (%) | 20 (5.3) | 36 (16.8) | 5 (5.3) | 8 (14.8) | 4 (4.2) | 10 (19.2) | 5 (5.4) | 13 (24.1) | 6 (6.3) | 5 (9.3) | OR 1.12 (0.50 to 2.51) (p = 0.70) |
OR 1.47 (0.68 to 3.18) (p = 0.32) | OR 0.89 (0.36 to 1.92) (p = 0.66) |
| Death within 90 days,n (%) | 23 (6.1) | 46 (21.5) | 5 (5.3) | 8 (14.8) | 5 (5.3) | 12 (23.1) | 7 (7.5) | 17 (31.5) | 6 (6.3) | 9 (16.7) | OR 1.41 (0.65 to 3.06) (p = 0.39) |
OR 2.11 (1.01 to 4.39) (p = 0.04) | OR 1.17 (0.53 to 2.58) (p = 0.70) |
Analyses were stratified on the disease severity at baseline (moderate: 7-point ordinal scale 3 or 4; severe: 7-point ordinal scale 5 or 6), and adjusted effect measures are reported in the table. Abbreviations: ECMO, Extracorporeal membrane oxygenation; HCQ, hydroxychloroquine; HR, hazard ratio; IFN, interferon; IQR, interquartile range; LRT, L/r, Lopinavir/ritonavir; lower respiratory tract; LSMD, least-square mean difference; NP, nasopharyngeal.