Abstract
Background: A growing number of randomized clinical trials (RCTs) provide promising data on pharmacokinetics/ pharmacodynamics, efficacy and safety of DOAC in children and the first DOACs have recently been approved for treatment of thromboembolism in children. Based on the risk benefit profiles published so far, we expect DOACs to be widely used for treatment and prophylaxis of thrombosis in children. The strict inclusion criteria for participation in the RCTs limit their generalizability, particularly to those with more serious acute and chronic medical conditions that account for a significant proportion of pediatric VTE patients in clinical practice. Real world data complements evidence from randomized clinical trials, and is urgently needed to improve patient care.
Aim: To obtain efficacy and safety data of DOACs in a large and heterogeneous pediatric patient collectives. To expand the knowledge on treatment strategies and outcomes across different risk profiles and comorbidities including cancer and renal disease.
Study Design: An international, multicentre, prospective observational cohort study imbedded in the Throm-PED Registry of the International Pediatric Thrombosis Network (IPTN). Parameters included at baseline are age, gender, height, weight, thrombosis type, thrombosis location, risk factors, underlying medical conditions and comedication. Primary outcomes include 1) thrombus progression or recurrence and 2) bleeding (major, clinically relevant non major including menorrhagia) and 3) mortality. Outcomes are assessed every 3 months for a total of 12 months. Additional variables include self-reported adherence, comedication, chemotherapy, DOAC drug levels, measures of renal function and dose adjustments on children with chronic medical conditions including renal disease and cancer.
Study population : Patients from 0-21 years with thromboembolic disease treated with DOACs who are enrolled in the IPTN Throm-PED Registry.
Results: As of June 30, 2021 82 patients from 10 centers have been enrolled. The majority of patients were at least 12 years old (Figure 1). 66% suffered from venous thrombosis. With about 30% each, pulmonary embolism or thrombosis of the lower extremities were reported most commonly. In this cohort the majority of patients received Rivaroxaban (80%), followed by Apixaban and Edoxaban. Risk factors were manifold, including patients with cancer (13%) and renal disease (4%). Of the 33 patients with follow-up reported at 3 months, bleeding was reported in 3 (9%) of patients during treatment with a DOAC, and thrombosis progression was reported in 2 (6%) (Table 1).
Summary: This initial real world data, as expected, demonstrates reduced efficacy and more bleeding than noted in published trials, however numbers are small. Further real world data collection is essential to identify specific patient groups at risk of worse outcome with DOACs and to understand drug interactions and dose adjustments. Data on younger age groups are required. IPTN registry is an important framework to collect real world data that can then be explored in clinical trials.
Figure 1 Figure 1.
Disclosures
Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy.
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