PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)—Rationale and Design

O’Brien, Sarah H.; Li, Danshi; Mitchell, Lesley; Heß, Thomas; Zee, Pamela; Yee, Donald L.; Newburger, Jane W.; Sung, Lillian; Rodriguez, Vilmarie

doi:10.1055/s-0039-1679938

Cited by 61 publications

(65 citation statements)

References 30 publications

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“…THROMBOTECT, a large open‐label randomized controlled trial comparing enoxaparin or antithrombin thromboprophylaxis to a control arm using unfractionated heparin (only during CVC use) in pediatric ALL patients during induction chemotherapy showed lower risk of VTE in the enoxaparin and antithrombin groups, with no difference in major hemorrhagic events between the three groups 37 . A randomized controlled trial of VTE prophylaxis with apixaban in pediatric ALL patients is underway, and results will help inform VTE prophylaxis in AYAO patients in the future 38 …”

Section: Discussionmentioning

confidence: 99%

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients

Hsiao

Krava

Wee

et al. 2021

Pediatric Blood & Cancer

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Background Venous thromboembolism (VTE) is a known complication among pediatric and adult cancer patients. Adolescent and young adult oncology (AYAO) patients have unique biological and physiological characteristics that make them distinct from other populations. Our objective was to study the VTE incidence, risk factors, and outcomes, which have been understudied in this population. Procedure A retrospective case–control study was conducted on AYAO participants with new or relapsed cancer and an imaging confirmed VTE from January 2011 to November 2016 at our institution. Eligible AYAO participants without a history of VTE were designated as controls and were randomly selected from our institution's tumor registry. Demographics, medical history, surgeries, central venous catheter (CVC) data, VTE diagnosis and treatment, relapses, and deaths were abstracted. Results Thirty‐five VTE cases and 70 controls were included in this analysis. Eighty percent of cases had leukemia or lymphoma (vs. a solid tumor) compared to 58% of controls. The majority of VTEs (57%) were CVC associated, and more than 70% of cases had more than one CVC placed during their cancer treatment versus 34% of controls. Infection was associated with increased VTE risk (OR = 6.35, 95% CI = 2.30, 17.55, p < .0001). VTE cases had increased cancer relapse (23% vs. 10%) and mortality rates (29% vs. 16%) than controls. Conclusion AYAO participants with a VTE were more likely to have leukemia or lymphoma, more than one CVC or infection. Further studies are needed to identify patients who would benefit from modifiable prevention measures, such as limiting to one CVC, preventing infections, or considering prophylactic anticoagulation for those with a liquid tumor.

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Section: Discussionmentioning

confidence: 99%

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients

Hsiao

Krava

Wee

et al. 2021

Pediatric Blood & Cancer

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“…To our knowledge, two trials are currently underway regarding this question which will respectively evaluate the effectiveness and safety of LMWH and apixaban in children with leukemia. 40,41 In summary, this systematic review and NMA of the current evidence suggests that LMWH is effective to prevent TE in children with cancer, compared with SOC. No statistically significant reduction in risk of TE was noted between AT replacement or VKA compared with SOC.…”

Section: Standard Of Carementioning

confidence: 86%

Effectiveness and Safety of Primary Thromboprophylaxis in Children with Cancer: A Systematic Review of the Literature and Network Meta-Analysis

et al. 2019

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Thromboembolism (TE) is a well-recognized complication of pediatric cancer and can lead to mortality and excess morbidity. There is conflicting evidence about the effectiveness and safety of thromboprophylaxis in children. We conducted a systematic literature review and network meta-analysis of primary pharmacological thromboprophylaxis in children and adolescents (0–21 years) with cancer. The primary outcomes were objectively proven TE and major bleeding. The network meta-analysis included comparisons of multiple alternatives simultaneously: antithrombin (AT) replacement, low molecular weight heparin (LMWH), vitamin K antagonists (VKAs), and standard of care (SOC) defined as no thromboprophylaxis or low-dose heparin for catheter patency. Six articles describing 1,318 patients were included (mean age: 6.7 years, 56.7% male). Acute lymphoblastic leukemia was the underlying diagnosis in 97.5% of patients. All studies were considered at moderate or high risk of bias. LMWH was the only agent associated with lower odds of TE compared with SOC (odds ratio [OR]: 0.23, 95% confidence interval [CI]: 0.06–0.81). No statistically significant difference was detected between other thromboprophylaxis modalities and SOC. Tau2 and I 2 suggested a high degree of heterogeneity. No statistically significant differences in the odds of major bleeding were found between AT replacement, LMWH, VKA, and SOC. Current evidence suggests that low-dose LMWH is effective and safe to prevent TE in children with cancer but is insufficient to conclude if AT replacement or VKA are effective thromboprophylaxis options. Further research, notably randomized controlled trials enrolling children with diverse types of cancer, is crucially needed.

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“…Despite multiple ongoing studies on apixaban in the pediatric population [12][13][14][15], there is currently no available data on apixaban pharmacokinetics and pharmacodynamics properties among children. As previously reported, the apixaban plasma concentration vs. time profile exhibited a multiphasic elimination profile, with an initial rapid decline followed by a more gradual terminal phase [4].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Accidental apixaban intoxication in a 23-month-old child: a case report

et al. 2020

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Background Direct oral anticoagulants, such as apixaban, are increasingly used in everyday practice in order to treat or prevent thromboembolic diseases. To date, there is no available data about apixaban pharmacokinetics in children, and no intoxication has previously been described. Case presentation A 23-month-old boy, with no medical history, was admitted to the emergency department 2 h after accidentally ingesting 40 mg apixaban and 0.75 mg digoxin. No adverse event was observed. Digoxin trough level was within therapeutic values. Apixaban blood concentration increased up to 1712 μg/L at H + 6 (1000–2750 μg/L using 2–5 mg/kg of apixaban in adults). The terminal half-life was 8.2 h (6–15 h in adults). The rapid elimination may explain the absence of bleeding despite high concentrations. Conclusions Despite an important intake of apixaban and a real disturbance in routine coagulation assays, no clinical sign of bleeding was observed, perhaps due to wide therapeutic range of apixaban. It may also be explained by its rapid elimination. Considering the high Cmax and a possible enteroenteric recycling, the use of activated charcoal should be considered in such situations in order to prevent eventual bleeding.

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PREVAPIX-ALL: Apixaban Compared to Standard of Care for Prevention of Venous Thrombosis in Paediatric Acute Lymphoblastic Leukaemia (ALL)—Rationale and Design

Cited by 61 publications

References 30 publications

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients

The incidence and risk factors for venous thromboembolism in adolescent and young adult oncology patients

Effectiveness and Safety of Primary Thromboprophylaxis in Children with Cancer: A Systematic Review of the Literature and Network Meta-Analysis

Accidental apixaban intoxication in a 23-month-old child: a case report

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