Summary of published pharmacological TP trials among hospitalized children
| Study . | Design . | Objective . | Patient population . | Intervention . | Outcomes . |
|---|---|---|---|---|---|
| Massicotte et al22 | Multicenter, open-label, randomized trial (PROTEKT) | Evaluate the efficacy and safety of reviparin-sodium for CVC-related VTE risk reduction | Children aged <18 y with new CVC | New CVC receive twice-daily reviparin-sodium or standard of care | VTE: 14.1% reviparin-sodium vs 12.5% standard-of-care group (OR, 1.15; 95% CI, 0.42-3.23; P = .82) Major bleeding: 0% reviparin-sodium vs 3.2% (P = 1) standard of care |
| Greiner et al23 | Multicenter, open-label, randomized trial (THROMBOTECT) | Evaluate the efficacy and safety of enoxaparin and antithrombin replacement for primary VTE prevention | Children aged <18 y treated on ALL-BFM 2000 or AIEOP-BFM 2009 | Enoxaparin with or without antithrombin vs low-dose UFH | Thromboembolism: UFH 8% vs enoxaparin 3.5% (P = .011) or antithrombin 1.9% (P < .001) |
| Faustino et al24 | Multicenter phase 2, open-label, blinded, end point trial (CRETE) | Evaluate the safety and exploratory efficacy of enoxaparin for primary prevention of CA-DVT | Children aged <18 years of age following insertion of a central venous catheter. | Enoxaparin targeting anti-Xa 0.2-0.5 IU/mL for CVC vs usual care | CA-DVT: 30.4% enoxaparin vs 54.2% usual care (RR, 0.55; 95% CI, 0.24-1.11). Clinically relevant CA-DVT 3.7% enoxaparin vs 29.2% usual care. Clinically relevant bleeding: 2.7% enoxaparin vs 0% usual care (P = 1). |
| McCrindle et al25 | Multicenter, open-label, randomized trial (UNIVERSE) | Evaluate the safety and efficacy of rivaroxaban for primary VTE prevention | Children aged <18 y following Fontan operation | Rivaroxaban vs aspirin | Thromboembolism: 2% rivaroxaban vs 9% aspirin CRNM: 6% rivaroxaban vs 9% aspirin |
| Portman et al26 | Phase 3, randomized, open-label, blinded, end point trial (ENNOBLE-ATE) | Evaluate the safety and efficacy of edoxaban for primary VTE prevention | Children aged <18 y with cardiac disease (congenital and acquired) requiring TE prevention | Edoxaban vs standard of care (VKA or enoxaparin) | Thromboembolism: 0% edoxaban vs 1.7% standard of care. Major or CRNM: 0.9% edoxaban vs 1.7% standard of care. |
| Sochet et al27 | Multicenter, phase 2, open-label trial (COVAC-TP) | Evaluate the safety and exploratory efficacy of enoxaparin for primary VTE prevention | Children aged <18 y with COVID-19 | Dose finding and efficacy | Patients with MIS-C required higher doses compared with COVID-19 (P = .01) 5.3% of patients developed provoked VTE. Clinically relevant bleeding: 0 (0%) |
| Payne et al28 | Phase 2, randomized, open-label trial (SAXOPHONE) | Evaluate the safety and efficacy of apixaban for primary VTE prevention | Children aged 28 days to <18 y with cardiac disease (congenital and acquired) requiring TE prevention | Apixaban vs standard of care (VKA or enoxaparin) | Thromboembolism: 0% apixaban vs 0% standard of care. CRNM bleeding: 0.8% apixaban vs 4.8% standard of care (% difference −4, 95% CI, −12.8 to 0.8). Concomitant aspirin: 38.9% in apixaban group, and 53.2% in standard-of-care group |
| Albisetti et al29 | Subanalysis of randomized, open-label, phase 2b/3 trial (DIVERSITY-CHD) | Evaluate the safety and efficacy of dabigatran for secondary VTE prevention | Children aged <18 y with congenital heart disease | Dabigatran vs standard of care for children with CHD | Primary end point: 81% dabigatran vs 59.3% standard of care, (OR, 0.34; 95% CI, 0.08-1.23). Major or CRNM bleeding 0%. |
| O’Brien et al30 | Multicenter, open-label, randomized, phase 3 trial (PREVAPIX-ALL) | Evaluate the efficacy and safety of apixaban for primary VTE prevention | ALL (pre-B cell or T cell) or lymphoblastic lymphoma (B-cell or T-cell immunophenotype) and a central venous line | Apixaban vs standard of care | VTE: 12% apixaban vs 18% standard of care (RR, 0.69; 95% CI, 0.45-1.05; P = .08) Major bleeding: 0.8% apixaban vs 0.8% standard of care (RR, 1; 95% CI, 0.14-7.01; P = 1). CRNM bleeding, 4% apixaban vs 1% standard of care; RR, 3.67; 95% CI, 1.04-12.97; P = .03). |
| Study . | Design . | Objective . | Patient population . | Intervention . | Outcomes . |
|---|---|---|---|---|---|
| Massicotte et al22 | Multicenter, open-label, randomized trial (PROTEKT) | Evaluate the efficacy and safety of reviparin-sodium for CVC-related VTE risk reduction | Children aged <18 y with new CVC | New CVC receive twice-daily reviparin-sodium or standard of care | VTE: 14.1% reviparin-sodium vs 12.5% standard-of-care group (OR, 1.15; 95% CI, 0.42-3.23; P = .82) Major bleeding: 0% reviparin-sodium vs 3.2% (P = 1) standard of care |
| Greiner et al23 | Multicenter, open-label, randomized trial (THROMBOTECT) | Evaluate the efficacy and safety of enoxaparin and antithrombin replacement for primary VTE prevention | Children aged <18 y treated on ALL-BFM 2000 or AIEOP-BFM 2009 | Enoxaparin with or without antithrombin vs low-dose UFH | Thromboembolism: UFH 8% vs enoxaparin 3.5% (P = .011) or antithrombin 1.9% (P < .001) |
| Faustino et al24 | Multicenter phase 2, open-label, blinded, end point trial (CRETE) | Evaluate the safety and exploratory efficacy of enoxaparin for primary prevention of CA-DVT | Children aged <18 years of age following insertion of a central venous catheter. | Enoxaparin targeting anti-Xa 0.2-0.5 IU/mL for CVC vs usual care | CA-DVT: 30.4% enoxaparin vs 54.2% usual care (RR, 0.55; 95% CI, 0.24-1.11). Clinically relevant CA-DVT 3.7% enoxaparin vs 29.2% usual care. Clinically relevant bleeding: 2.7% enoxaparin vs 0% usual care (P = 1). |
| McCrindle et al25 | Multicenter, open-label, randomized trial (UNIVERSE) | Evaluate the safety and efficacy of rivaroxaban for primary VTE prevention | Children aged <18 y following Fontan operation | Rivaroxaban vs aspirin | Thromboembolism: 2% rivaroxaban vs 9% aspirin CRNM: 6% rivaroxaban vs 9% aspirin |
| Portman et al26 | Phase 3, randomized, open-label, blinded, end point trial (ENNOBLE-ATE) | Evaluate the safety and efficacy of edoxaban for primary VTE prevention | Children aged <18 y with cardiac disease (congenital and acquired) requiring TE prevention | Edoxaban vs standard of care (VKA or enoxaparin) | Thromboembolism: 0% edoxaban vs 1.7% standard of care. Major or CRNM: 0.9% edoxaban vs 1.7% standard of care. |
| Sochet et al27 | Multicenter, phase 2, open-label trial (COVAC-TP) | Evaluate the safety and exploratory efficacy of enoxaparin for primary VTE prevention | Children aged <18 y with COVID-19 | Dose finding and efficacy | Patients with MIS-C required higher doses compared with COVID-19 (P = .01) 5.3% of patients developed provoked VTE. Clinically relevant bleeding: 0 (0%) |
| Payne et al28 | Phase 2, randomized, open-label trial (SAXOPHONE) | Evaluate the safety and efficacy of apixaban for primary VTE prevention | Children aged 28 days to <18 y with cardiac disease (congenital and acquired) requiring TE prevention | Apixaban vs standard of care (VKA or enoxaparin) | Thromboembolism: 0% apixaban vs 0% standard of care. CRNM bleeding: 0.8% apixaban vs 4.8% standard of care (% difference −4, 95% CI, −12.8 to 0.8). Concomitant aspirin: 38.9% in apixaban group, and 53.2% in standard-of-care group |
| Albisetti et al29 | Subanalysis of randomized, open-label, phase 2b/3 trial (DIVERSITY-CHD) | Evaluate the safety and efficacy of dabigatran for secondary VTE prevention | Children aged <18 y with congenital heart disease | Dabigatran vs standard of care for children with CHD | Primary end point: 81% dabigatran vs 59.3% standard of care, (OR, 0.34; 95% CI, 0.08-1.23). Major or CRNM bleeding 0%. |
| O’Brien et al30 | Multicenter, open-label, randomized, phase 3 trial (PREVAPIX-ALL) | Evaluate the efficacy and safety of apixaban for primary VTE prevention | ALL (pre-B cell or T cell) or lymphoblastic lymphoma (B-cell or T-cell immunophenotype) and a central venous line | Apixaban vs standard of care | VTE: 12% apixaban vs 18% standard of care (RR, 0.69; 95% CI, 0.45-1.05; P = .08) Major bleeding: 0.8% apixaban vs 0.8% standard of care (RR, 1; 95% CI, 0.14-7.01; P = 1). CRNM bleeding, 4% apixaban vs 1% standard of care; RR, 3.67; 95% CI, 1.04-12.97; P = .03). |
CA-DVT, catheter-associated DVT; CHD, congenital heart disease; CI, confidence interval; CRNM, clinically relevant nonmajor; OR, odds ratio; RR, relative risk; UFH, unfractionated heparin; VKA, vitamin K antagonist.