Anticoagulant therapy for 6 weeks is noninferior to 3 months for provoked VTE in patients younger than 21 years (Kids-DOTT)

Reference

Goldenberg NA, Kittelson JM, Abshire TC, et al, for the Kids-DOTT Trial Investigators and the ATLAS Group. Effect of anticoagulant therapy for 6 weeks vs 3 months on recurrence and bleeding events in patients younger than 21 years of age with provoked venous thromboembolism. The Kids-DOTT randomized clinical trial. JAMA 2022;327(2):129-137.

Synopsis

Standard treatment for adults with provoked venous thromboembolism (provoked VTE; ie, temporally associated with a prothrombotic clinical risk factor) is 3 months of anticoagulant therapy. Whether this same duration is necessary for children is uncertain. These investigators identified patients younger than 21 years with an acute VTE diagnosed via standard imaging modalities and a provoking factor, including recent hospitalization, traumatic injury, or central venous catheterization. Exclusion criteria included history of VTE, active malignancy, systemic lupus erythematosus, isolated pulmonary embolism, and deficiencies of natural anticoagulants (ie, protein C, protein S, antithrombin). All participants initially received standard treatment with intravenous unfractionated heparin or subcutaneous low-molecular-weight (LMW) heparin followed by LMW heparin, fondaparinux, oral vitamin K antagonists, or direct oral anticoagulants. At 6 weeks, all patients underwent repeat imaging. Similarly, those patients initially noted at baseline to have antiphospholipid antibodies underwent follow-up testing. Those patients (n = 417) with venous flow occurring in the involved vessel segments and without persistent antiphospholipid antibodies randomly received (concealed allocation) assignment to either discontinue anticoagulant therapy or to continue anticoagulant therapy for a total of 3 months. Individuals assessing outcomes remained masked to treatment group assignment. Complete follow-up occurred for 89.9% of patients at 1 year. Using both intention-to-treat and per-protocol analyses, the primary outcome (recurrent VTE within 1 year) occurred less frequently in the 6-week group than in the 3-month group (0.97% vs 1.91% and 0.65% vs 1.40%, respectively). The primary safety outcome — clinically relevant bleeding events — also occurred less frequently in the 6-week group than in the 3-month group (0.65% vs 0.70% and 0.97% vs 2.38%, respectively). All outcomes met predetermined criteria for noninferiority. Similarly, other secondary outcomes, such as chronic venous insufficiency, occurred similarly in both treatment groups.