Primary, secondary, and exploratory outcomes for modified intent-to-treat population of activated patients and safety outcomes
| . | TXA . | Placebo . | Estimate . | 95% CI . | P value . |
|---|---|---|---|---|---|
| N | 165 | 165 | |||
| Primary endpoint | |||||
| Any grade 2+ bleed,* n/N (%) | 73/145 (50.3) | 78/144 (54.2) | OR = 0.83† | 0.50-1.34† | .44† |
| Secondary endpoints | |||||
| Platelet transfusions, mean (SD) | 7.7 (8.7) | 7.6 (10.1) | MD = 0.07† | −1.90 to 2.04† | .95† |
| D without grade 2+ bleed,‡ mean (SD) [n] | 28.1 (3.7) [136] | 27.7 (4.7) [132] | MD = 0.79† | −0.40 to 1.98† | .19† |
| Exploratory endpoints | |||||
| D with bleeding or thrombocytopenia, mean (SD) [n] | 9.5 (6.8) [133] | 9.5 (6.4) [128] | MD = 0.04 | −1.32 to 1.39 | .96 |
| D until 2+ bleed or death, mean (SD)§ | 19.6 (0.9) | 19.9 (0.9) | HR = 0.94 | 0.68-1.29 | .70 |
| Highest grade bleed,ǁ mean (SD) | 1.4 (0.8) | 1.4 (0.8) | MD = 0.00 | -0.15 to 0.16 | .95 |
| Death due to bleeding, n/N (%) | 0/165 (0.0) | 0/165 (0.0) | OR = 1.00 | 0.81-1.24 | 1.00 |
| Exploratory endpoints, transfusions (complete data only) | |||||
| Platelet transfusion per thrombocytopenic day,¶ mean (SD) [n] | 1.0 (0.3) [153] | 1.0 (0.4) [151] | MD = −0.04 | −0.12 to 0.04 | .33 |
| RBC transfusion per thrombocytopenic day,¶ mean (SD) [n] | 0.4 (0.4) [153] | 0.4 (0.4) [151] | MD = 0.03 | −0.06 to 0.12 | .50 |
| Survived 30 d without platelet transfusion, n/N (%) | 2/164 (1.2) | 4/163 (2.5) | OR = 0.50 | 0.09-2.81 | .43 |
| Survived 30 d without RBC transfusion, n/N (%) | 12/164 (7.3) | 12/163 (7.4) | OR = 1.04 | 0.44-2.46 | .94 |
| Platelet nadir over 10 000/µL, n/N (%) | 12/165 (7.3) | 14/165 (8.5) | OR = 0.85 | 0.38-1.90 | .69 |
| Safety# | |||||
| Thrombotic events in 120 d, N | 163 | 163 | |||
| Mean (SD) | 0.3 (0.8) | 0.2 (0.6) | |||
| VOD in 30 d of last dose, n/N (%) | 3/163 (1.8) | 2/163 (1.2) | |||
| All-cause mortality, n/N (%) | 4/163 (2.5) | 5/163 (3.1) | |||
| All-cause mortality in 120 d, n/N (%) | 19/163 (11.7) | 19/163 (11.7) | |||
| Death due to thrombosis in 120 d, n/N (%) | 0/163 (0.0) | 0/163 (0.0) | |||
| Subgroups** | |||||
| WHO grade 2+ bleeding within disease group,*,† | |||||
| Allogeneic transplant | 57.6%† | 58.6%† | 0.96† | 0.46-2.00† | |
| Autologous transplant | 17.1%† | 23.8%† | 0.62† | 0.19-2.08† | |
| Chemotherapy | 48.0%† | 52.0%† | 0.84† | 0.40-1.76† |
| . | TXA . | Placebo . | Estimate . | 95% CI . | P value . |
|---|---|---|---|---|---|
| N | 165 | 165 | |||
| Primary endpoint | |||||
| Any grade 2+ bleed,* n/N (%) | 73/145 (50.3) | 78/144 (54.2) | OR = 0.83† | 0.50-1.34† | .44† |
| Secondary endpoints | |||||
| Platelet transfusions, mean (SD) | 7.7 (8.7) | 7.6 (10.1) | MD = 0.07† | −1.90 to 2.04† | .95† |
| D without grade 2+ bleed,‡ mean (SD) [n] | 28.1 (3.7) [136] | 27.7 (4.7) [132] | MD = 0.79† | −0.40 to 1.98† | .19† |
| Exploratory endpoints | |||||
| D with bleeding or thrombocytopenia, mean (SD) [n] | 9.5 (6.8) [133] | 9.5 (6.4) [128] | MD = 0.04 | −1.32 to 1.39 | .96 |
| D until 2+ bleed or death, mean (SD)§ | 19.6 (0.9) | 19.9 (0.9) | HR = 0.94 | 0.68-1.29 | .70 |
| Highest grade bleed,ǁ mean (SD) | 1.4 (0.8) | 1.4 (0.8) | MD = 0.00 | -0.15 to 0.16 | .95 |
| Death due to bleeding, n/N (%) | 0/165 (0.0) | 0/165 (0.0) | OR = 1.00 | 0.81-1.24 | 1.00 |
| Exploratory endpoints, transfusions (complete data only) | |||||
| Platelet transfusion per thrombocytopenic day,¶ mean (SD) [n] | 1.0 (0.3) [153] | 1.0 (0.4) [151] | MD = −0.04 | −0.12 to 0.04 | .33 |
| RBC transfusion per thrombocytopenic day,¶ mean (SD) [n] | 0.4 (0.4) [153] | 0.4 (0.4) [151] | MD = 0.03 | −0.06 to 0.12 | .50 |
| Survived 30 d without platelet transfusion, n/N (%) | 2/164 (1.2) | 4/163 (2.5) | OR = 0.50 | 0.09-2.81 | .43 |
| Survived 30 d without RBC transfusion, n/N (%) | 12/164 (7.3) | 12/163 (7.4) | OR = 1.04 | 0.44-2.46 | .94 |
| Platelet nadir over 10 000/µL, n/N (%) | 12/165 (7.3) | 14/165 (8.5) | OR = 0.85 | 0.38-1.90 | .69 |
| Safety# | |||||
| Thrombotic events in 120 d, N | 163 | 163 | |||
| Mean (SD) | 0.3 (0.8) | 0.2 (0.6) | |||
| VOD in 30 d of last dose, n/N (%) | 3/163 (1.8) | 2/163 (1.2) | |||
| All-cause mortality, n/N (%) | 4/163 (2.5) | 5/163 (3.1) | |||
| All-cause mortality in 120 d, n/N (%) | 19/163 (11.7) | 19/163 (11.7) | |||
| Death due to thrombosis in 120 d, n/N (%) | 0/163 (0.0) | 0/163 (0.0) | |||
| Subgroups** | |||||
| WHO grade 2+ bleeding within disease group,*,† | |||||
| Allogeneic transplant | 57.6%† | 58.6%† | 0.96† | 0.46-2.00† | |
| Autologous transplant | 17.1%† | 23.8%† | 0.62† | 0.19-2.08† | |
| Chemotherapy | 48.0%† | 52.0%† | 0.84† | 0.40-1.76† |
Unless otherwise indicated, endpoint measures within 30 days of activation (whether or not on the drug), OR adjusted for study site and disease group.
HR, hazard ratio; MD, difference of means; OR, odds ratio; RBC, red blood cells; VOD, veno-occlusive disease.
The WHO grading system was used to determine the severity of bleeding (supplemental File 2, Appendix A).
Analysis based on imputed data.
Includes all days without a bleed of grade ≥2, both days before a bleed occurs and after it resolves. Many patients experienced multiple severe bleeds.
Restricted mean and restricted standard deviation from time of activation until 30 days based on Kaplan-Meier curves.
A list of grade 3 and grade 4 bleeds and their sites is provided in supplemental File 2, Appendix G.
For a given subject, we calculated the days with thrombocytopenia (<10 000 per µL) and (a) platelet transfusions or (b) RBC transfusions or (c) any bleeding out of the total number of thrombocytopenic days. These proportions are then summarized across patients.
Uses safety population (all patients who received study drug).
A prespecified subgroup of those with and without bleeding at baseline was not analyzed or reported due to small numbers.