Table 2.
Primary and secondary outcomes of moderately ill patients with covid-19 admitted to hospital wards, according to treatment assignment
| Outcomes | No (%) of patients | Odds ratio or geometric mean ratio (95% CI) | P value | |
|---|---|---|---|---|
| Therapeutic heparin (n=228) | Prophylactic heparin (n=237) | |||
| Primary outcome | ||||
| Primary composite outcome* | 37 (16.2) | 52 (21.9) | 0.69 (0.43 to 1.10) | 0.12 |
| Secondary outcomes | ||||
| Death from any cause | 4 (1.8) | 18 (7.6) | 0.22 (0.07 to 0.65) | 0.006 |
| Invasive mechanical ventilation | 11 (4.8) | 16 (6.8) | 0.70 (0.32 to 1.55) | 0.38 |
| Any mechanical ventilation† | 21 (9.2) | 26 (11.0) | 0.82 (0.45 to 1.51) | 0.53 |
| ICU admission | 33 (14.5) | 42 (17.7) | 0.79 (0.48 to 1.29) | 0.34 |
| Death or any mechanical ventilation | 23 (10.1) | 38 (16.0) | 0.59 (0.34 to 1.02) | 0.06 |
| Death or ICU admission | 36 (15.8) | 50 (21.1) | 0.70 (0.44 to 1.13) | 0.14 |
| Mean (SD) ventilator-free days | 26.5 (5.6) | 24.7 (8.5) | 1.77 (1.02 to 3.08) | 0.042 |
| Mean (SD) organ support-free days | 25.8 (6.2) | 24.1 (8.8) | 1.41 (0.90 to 2.21) | 0.13 |
| Mean (SD) ICU-free days | 26.0 (6.1) | 24.2 (8.8) | 1.51 (0.94 to 2.41) | 0.087 |
| Mean (SD) hospital-free days | 19.8 (7.3) | 18.4 (9.2) | 1.09 (0.79 to 1.50) | 0.59 |
| Renal replacement therapy‡ | 2 (0.9) | 5 (2.1) | 0.41 (0.08 to 2.15) | 0.29 |
| Thromboembolism§: | ||||
| Venous | 2 (0.9) | 6 (2.5) | 0.34 (0.07 to 1.71) | 0.19 |
| Arterial | 0 (0.0) | 1 (0.4) | - | - |
| Bleeding: | ||||
| ISTH major bleeding¶ | 2 (0.9) | 4 (1.7) | 0.52 (0.09 to 2.85) | 0.69 |
| Red blood cell transfusion (≥1 unit) | 3 (1.3) | 9 (3.8) | 0.34 (0.09 to 1.27) | 0.14 |
| Transfusion of other blood components or products** | 1 (0.4) | 0 (0.0) | - | - |
| Heparin induced thrombocytopenia | 0 (0.0) | 0 (0.0) | - | - |
| Geometric mean (SD) D-dimer ratio (D-dimer×ULN)†† | 1.9 (0.7) | 2.4 (0.9) | 0.88 (0.78 to 0.99) | 0.032 |
ICU=intensive care unit; SD=standard deviation; ISTH=International Society on Thrombosis and Haemostasis.
All clinical outcomes were assessed up to 28 days post-randomisation. Analyses of all outcomes with exception of D-dimer ratio (D-dimer×ULN), ventilator-free, organ support-free, ICU-free, and hospital-free days alive were repeated for the timeframe up to hospital discharge and are shown in supplementary table S20.
Defined as death, invasive mechanical ventilation, non-invasive mechanical ventilation, or ICU admission.
Invasive or non-invasive (bilevel or continuous positive airway pressure) mechanical ventilation.
Continuous renal replacement therapy or intermittent haemodialysis.
All diagnostically confirmed except for one symptomatic deep vein thrombosis event in the prophylactic heparin group, which could not be definitively confirmed because diagnostic imaging was not done during acute symptomatic period.
Major bleeding defined by the ISTH Scientific and Standardization Committee.
Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipitate and/or fibrinogen concentrate; 17 patients received convalescent plasma and were not included in the count.
Geometric mean ratio defined as ratio of geometric means of D-dimer ratios (D-dimer×ULN) of day 2 ±24 hours post-randomisation, adjusted for baseline geometric means of D-dimer ratios using analysis of covariance. SD for the natural logarithm of D-dimer ratios at day 2 ±24 hours. Data for day 2 ±24 hours D-dimer were missing for 66 patients in the therapeutic heparin group and 64 in the prophylactic heparin group.