Table 2.
End Points in the Primary Analysis Population.*
| End Point | Vitamin D (N = 538) | Placebo (N = 540) | P Value or Difference (95% CI) | ||
|---|---|---|---|---|---|
| Value | No. of Patients with Data | Value | No. of Patients with Data | ||
| Primary end point | |||||
| Death from any cause in any location to day 90 — no. (%) | 125 (23.5) | 531 | 109 (20.6) | 528 | 0.26 |
| Secondary clinical end points | |||||
| Death from any cause in any location to day 28 — no. (%) | 92 (17.3) | 531 | 69 (13.1) | 528 | 4.3 (−0.1 to 8.6) |
| Death in the hospital to day 90 — no. (%) | 92 (17.1) | 538 | 72 (13.4) | 539 | 3.7 (−0.5 to 8.0) |
| Alive and at home under previous level of care at day 90 — no. (%) | 348 (65.9) | 528 | 345 (65.6) | 526 | 0.3 (−5.4 to 6.0) |
| Hospital length of stay to day 90 — days | |||||
| Mean ±SD | 9.1±9.2 | 406 | 10.4±11.0 | 418 | −1.4 (−2.7 to 0.0) |
| Mean ±SE† | 9.0±0.4 | 406 | 9.9±0.4 | 418 | −0.9 (−1.9 to 0.1) |
| Discharged to other health care facility — no. (%) | 71 (17.5) | 406 | 89 (21.2) | 419 | −3.8 (−9.1 to 1.6) |
| Health care facility length of stay — days | |||||
| Mean ±SD | 6.0±17.5 | 402 | 8.1±20.4 | 416 | −2.2 (−4.8 to 0.4) |
| Mean ±SE† | 5.5±0.7 | 402 | 7.5±0.7 | 416 | −1.9 (−3.8 to −0.1) |
| Mean ±SD ventilator-free days to day 28 | 21.3±11.3 | 523 | 22.1±10.5 | 534 | −0.8 (−2.1 to 0.5) |
| Change in EQ-5D-5L from baseline to day 90 | |||||
| Mean ±SD | 0.0±0.2 | 340 | 0.0±0.2 | 346 | 0.0 (0.0 to 0.1) |
| Mean ±SE† | 0.0±0.0 | 340 | 0.0±0.0 | 346 | 0.0 (0.0 to 0.1) |
| Secondary physiological end points | |||||
| New, postrandomization mechanical ventilation — no. (%) | 39 (10.7) | 365 | 29 (8.2) | 354 | 2.5 (−1.8 to 6.8) |
| Mean ±SD lowest Pao2:Fio2 to day 7 | 179.8±102.6 | 122 | 185.8±110.4 | 136 | −5.9 (−32.2 to 20.3) |
| New ARDS to day 7 — no. (%) | 20 (4.9) | 411 | 17 (4.1) | 412 | 0.7 (−2.1 to 3.6) |
| ARDS severity to day 7 — no. (%) | |||||
| Mild | 6 (30.0) | 20 | 4 (23.5) | 17 | 6.5 (−22.0 to 34.9) |
| Moderate | 9 (45.0) | 20 | 12 (70.6) | 17 | −25.6 (−56.3 to 5.1) |
| Severe | 5 (25.0) | 20 | 1 (5.9) | 17 | 19.1 (−2.9 to 41.1) |
| Worst severity of acute kidney injury to day 7 — no. (%) | |||||
| None | 285 (58.9) | 484 | 297 (60.0) | 495 | −1.1 (−7.3 to 5.0) |
| Mild | 70 (14.5) | 484 | 77 (15.6) | 495 | −1.1 (−5.6 to 3.4) |
| Moderate | 48 (9.9) | 484 | 52 (10.5) | 495 | −0.6 (−4.4 to 3.2) |
| Severe | 81 (16.7) | 484 | 69 (13.9) | 495 | 2.8 (−1.7 to 7.3) |
| New renal-replacement therapy to day 7 — no. (%) | 20 (4.1) | 489 | 18 (3.6) | 500 | 0.5 (−1.9 to 2.9) |
| Mean ±SE highest creatinine level to day 7 — mg/dl‡ | 2.2±0.1 | 518 | 2.1±0.1 | 528 | 0.0 (−0.2 to 0.1) |
| New vasopressor use to day 7 — no. (%) | 43 (12.0) | 357 | 42 (11.7) | 360 | 0.4 (−4.4 to 5.1) |
| Mean ±SE highest cardiovascular SOFA score to day 7‡ | 1.4±0.1 | 523 | 1.3±0.1 | 534 | −0.1 (−0.3 to 0.0) |
| Mean ±SD 25-hydroxyvitamin D level at day 3 — ng/ml | 46.9±23.2 | 145 | 11.4±5.6 | 133 | 35.5 (31.5 to 39.6) |
| 25-Hydroxyvitamin D level category at day 3 — no. (%) | |||||
| <20 ng/ml | 18 (12.4) | 145 | 125 (94.0) | 133 | −81.6 (−88.3 to −74.9) |
| 20 to <30 ng/ml | 18 (12.4) | 145 | 8 (6.0) | 133 | 6.4 (−0.3 to 13.1) |
| 30 to <120 ng/ml | 108 (74.5) | 145 | 0 | 133 | 74.5 (67.4 to 81.6) |
| ≥120 ng/ml | 1 (0.7) | 145 | 0 | 133 | 0.7 (−0.7 to 2.0) |
| Mean ±SD interleukin-6 level at day 3 — pg/ml | 216±1574 | 141 | 298±2219 | 125 | −82 (−543 to 378) |
| Secondary safety end points | |||||
| Serious adverse events — no. | 13 | 17 | 0.47 | ||
| Hypercalcemia to day 14 — no. (%) | 14 (2.7) | 513 | 11 (2.1) | 523 | 0.51 |
| Mean ±SD highest total calcium level to day 14 — mg/dl | 8.9±0.8 | 507 | 8.8±0.7 | 513 | 0.004 |
| Mean ±SD highest ionized calcium level to day 14 — mg/dl | 4.7±0.8 | 153 | 4.6±0.8 | 177 | 0.67 |
| Kidney stones to day 90 — no. (%) | 0 | 507 | 3 (0.6) | 507 | 0.25 |
| Falls to day 90 — no. (%) | 36 (7.1) | 507 | 27 (5.3) | 507 | 0.24 |
| Fall-related fractures to day 90 — no. (%) | 4 (0.8) | 507 | 2 (0.4) | 507 | 0.69 |
*
To convert the values for calcium to millimoles per liter, multiply by 0.250. Pao2:Fio2 denotes the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen.
†
Values were calculated from a survivor average causal effect model.
‡
Cardiovascular SOFA scores range from 0 to 4, with higher scores indicating more severe organ failure. Values were controlled for the baseline value with the use of repeated-measures analysis of variance with a treatment-by-time interaction and shared intercept at baseline.