Clinical practice guidelines suggest a six-week course of anticoagulant therapy for pediatric venous thromboembolism instead of the three-month course recommended for adults, but there is a need for definitive evidence to support this recommendation. A randomized clinical trial was designed to test the hypothesis that a six-week course of anticoagulant therapy in patients younger than 21 years of age who had a provoked venous thromboembolism is noninferior to a three-month course of therapy.

The multinational trial enrolled patients younger than age 21 who had radiologically confirmed acute provoked venous thromboembolism. The main exclusion criteria were prior venous thromboembolism and clinically significant anticoagulant deficiencies. At six-week follow-up, patients with venous flow evident in the involved vessel segments and without persistent antiphospholipid antibodies were randomized to discontinuation of anticoagulants or continuation for a total of three months after diagnosis.

Among the 297 patients in the per-protocol population (median age, 8.3 years), the primary efficacy outcome (adjudicated symptomatic recurrent venous thromboembolism within one year) occurred in one patient (0.65%) in the six-week treatment group and in two patients (1.40%) in the three-month group. The primary safety outcome (adjudicated clinically relevant bleeding events within one year) occurred in one patient (0.65%) in the six-week group and one patient (0.70%) in the three-month group. Based on the absolute risk differences between groups, noninferiority was demonstrated. Adverse events occurred in 26% of patients in the six-week treatment group and in 32% of those in the three-month group.

The study population was characterized by a small proportion of people who had cancer or pulmonary embolism, so the results may not apply to these patient populations. Also, although most patients received low-molecular-weight heparin, direct oral anticoagulants are increasingly used for pediatric venous thromboembolism.

The authors point out that the low rates of recurrent venous thromboembolism they observed support shortening the duration of anticoagulant therapy for provoked venous thromboembolism in patients younger than age 21.