Table 2. Primary Outcome, Key Secondary Outcomes, and Safety Outcomes in the TXA-127 Trial and in the TRV-027 Trial.
| TXA-127 trial | TRV-027 trial | |||||||
|---|---|---|---|---|---|---|---|---|
| TXA-127 (n = 170) | Placebo (n = 173) | Unadjusted absolute difference (95% CrI)a | Adjusted OR (95% CrI)b |
TRV-027 (n = 145) | Placebo (n = 145) | Unadjusted absolute difference (95% CrI)a | Adjusted OR (95% CrI)b |
|
| Primary outcome | ||||||||
| Oxygen-free days at 28 d, mean (SD)c | 9.0 (10.9) | 11.3 (11.5) | −2.3 (−4.8 to 0.2) | 0.88 (0.59 to 1.30) | 8.1 (10.8) | 10.5 (11.5) | −2.4 (−5.1 to 0.3) | 0.74 (0.48 to 1.13) |
| Key secondary outcomes d | ||||||||
| Mortality at 28 d, No./total (%) | 22/163 (13.5) | 22/166 (13.3) | 0.2 (−7.1 to 7.6) | 0.83 (0.41 to 1.66) | 29/141 (20.6) | 18/140 (12.9) | 7.7 (−0.9 to 16.4) | 1.52 (0.75 to 3.08) |
| Alive and free from respiratory failure at 28 d, No./total (%)e | 123/155 (79.4) | 125/160 (78.1) | 1.2 (−7.8 to 10.2) | 1.43 (0.78 to 2.63) | 96/136 (70.6) | 106/136 (77.9) | −7.4 (−17.7 to 3.0) | 0.88 (0.47 to 1.66) |
| WHO COVID-19 clinical progression level at 28 d, No. (%)f | (n = 154) | (n = 158) | (n = 135) | (n = 134) | ||||
| 1 | 58 (37.7) | 62 (39.2) | −1.6 (−12.3 to 9.2) | 0.88 (0.58 to 1.35) | 48 (35.6) | 47 (35.1) | 0.5 (−10.9 to 11.9) | 0.97 (0.62 to 1.53) |
| 2 | 53 (34.4) | 58 (36.7) | −2.3 (−12.9 to 8.3) | 44 (32.6) | 53 (39.6) | −7.0 (−18.3 to 4.5) | ||
| 3 | 4 (2.6) | 2 (1.3) | 1.3 (−1.6 to 4.6) | 0 | 2 (1.5) | NE | ||
| 4 | 7 (4.6) | 1 (0.6) | 3.9 (0.8 to 7.8) | 3 (2.2) | 2 (1.5) | 0.7 (−2.5 to 4.2) | ||
| 5 | 1 (0.7) | 3 (1.9) | −1.2 (−4.0 to 1.1) | 3 (2.2) | 3 (2.2) | 0 (−3.7 to 3.6) | ||
| 6 | 4 (2.6) | 5 (3.2) | −0.6 (−4.4 to 3.2) | 3 (2.2) | 4 (3.0) | −0.8 (−4.7 to 3.0) | ||
| 7 | 5 (3.3) | 5 (3.2) | 0.1 (−3.9 to 4.1) | 5 (3.7) | 5 (3.7) | 0 (−4.6 to 4.6) | ||
| 8 | 22 (14.3) | 22 (13.9) | 0.4 (−7.3 to 8.1) | 29 (21.5) | 18 (13.4) | 8.0 (−0.9 to 17.1) | ||
| Safety outcomes, No. (%) g | ||||||||
| ≥1 Hypotensive event through 7 d | 19 (11.2) | 21 (12.1) | −1.0 (−7.7 to 5.8) | 0.66 (0.31 to 1.38) | 21 (14.5) | 16 (11.0) | 3.4 (−4.2 to 11.2) | 1.04 (0.48 to 2.25) |
| New kidney replacement therapy through 28 d | 11 (6.5) | 12 (6.9) | −0.5 (−5.8 to 4.9) | 0.75 (0.31 to 1.84) | 9 (6.2) | 11 (7.6) | −1.4 (−7.3 to 4.4) | 0.59 (0.22 to 1.56) |
| Allergic reaction through 7 d | 3 (<1) | 0 | NE | NE | 0 | 0 | NE | NE |
Abbreviations: OR, odds ratio; CrI, credible interval; NE, not estimable; WHO, World Health Organization.
Calculated using normal distribution with a flat prior for both the mean and variance for oxygen-free days, excluding partially observed values. A binomial distribution with an improper β prior was used for each binary outcome.
The adjusted ORs were calculated using regression techniques with covariable adjustment for age group, sex, and baseline level on the WHO COVID-19 clinical progression ordinal scale. For oxygen-free days at 28 days, multivariable proportional odds was used (adjusted OR <1.0 is the direction of inferiority for the active agent); for mortality at 28 days, multivariable logistic regression was used (OR <1.0 is the direction of superiority for the active agent); for alive and free from respiratory failure at 28 days, multivariable logistic regression was used (OR <1.0 is the direction of inferiority for the active agent); for WHO COVID-19 clinical progression level at 28 days, multivariable proportional odds was used (OR <1.0 is the direction of superiority for the active agent); for all safety outcomes, multivariable logistic regression was used (OR <1.0 is the direction of fewer safety events for the active group).
Calculated as 28 days minus the number of days between initiation and final liberation from new supplemental oxygen use during the 28 days after randomization. Patients who died before day 28 were coded as having −1 oxygen-free days (worst possible outcome). The primary analysis of oxygen-free days included all patients, including those with partially observed data (ie, patients for whom the number of oxygen-free days was not known precisely but was known to be within a certain range). In the TXA-127 trial, there were 17 patients with partially observed data in the TXA-127 group and 18 patients in the placebo group. In the TRV-027 trial, there were 10 patients with partially observed data in the TRV-027 group and 14 patients in the placebo group. The mean (SD) estimates exclude patients with partially observed oxygen-free days.
Additional secondary and safety outcomes appear in eTables 13-18 in Supplement 1. The outcomes presented in this Table plus those in eTables 13-18 in Supplement 1 are an exhaustive list of prespecified outcomes for the trials.
Defined as alive and not requiring high-flow nasal oxygen, noninvasive ventilation, or invasive ventilation.
Eight-level ordinal scale representing the worst patient clinical status on a given day. Level 1 was defined as ambulatory and not hospitalized, no limitation of activities; level 2, ambulatory and not hospitalized with limitation of activities or home oxygen therapy; level 3, hospitalized with mild disease, not receiving oxygen therapy; level 4, hospitalized with mild disease and receiving oxygen by mask or nasal prongs; level 5, hospitalized with severe disease and receiving noninvasive ventilation or high-flow oxygen; level 6, hospitalized with severe disease and receiving invasive mechanical ventilation; level 7, hospitalized with severe disease and receiving invasive mechanical ventilation plus additional organ support with vasopressors, kidney replacement therapy or extracorporeal membrane oxygenation; and level 8, dead.
Prespecified and data were collected by clinicians blinded to treatment assignment in real time.