Multicenter, Open-Label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of an age-and-body Weight-adjusted Rivaroxaban Regimen Compared to Standard of Care in Children with Acute Venous Thromboembolism
Study ID: STU 062015-073
Children aged 6 months to [Less Than] 18 years with confirmed acute venous thromboembolism who receive initial treatment with therapeutic dosages of unfractionated heparin (uFH), low molecular weight heparin (LMWH), or fondaparinux are potentially eligible for the study. initial treatment with uFH, LMWH or fondaparinux will be administered for at least 5 days. The study will be divided into 4 age groups: 12 yrs and less than 18 years; 6 yrs and less than 12 yrs; 2 yrs and less than 6 yrs 6 months to less than 2 yrs. This is a multicenter, open-label, active-controlled, randomized study to evaluate the efficacy and safety of an age- and body weight-adjusted rivaroxaban regimen in children with acute venous thromboembolism. Randomization can be done during the first 9 days of initial treatment and will be in a 2 (rivaroxaban): 1 (standard of care [SoC]) fashion. Children randomized to rivaroxaban will start rivaroxaban the day following the last administration of initial therapy with uFH, LMWH, or fondaparinux but with a minimal duration of initial therapy of 5 days and a maximum duration of 9 days. The first administration of rivaroxaban will be started: * 4 hours after discontinuation of uFH * 12 hours after discontinuation of LMWH with a b.i.d. regimen, and * 24 hours after discontinuation of fondaparinux or LMWH with an o.d. regimen. Children randomized to standard of care can continue uFH, LMWH, or fondaparinux or can switch to VKa therapy. if VKa therapy is planned, it can be initiated any time after randomization. initial therapy with uFH, LMWH, or fondaparinux can be stopped after a minimum of 5 days and only if the inR is above 2 on two separate occasions, 24 hours apart. after randomization, children will receive either rivaroxaban or comparator for a main study treatment period of 3 months. after the main study treatment period of 3 months, the diagnostic imaging test which was obtained at baseline will be repeated, if clinically feasible and the decision is made to stop study treatment or to continue for an additional 3 months. in children who completed 6 months of treatment, the decision is made to stop study treatment or to continue for an additional 3 months. Then, in children who completed 9 months of treatment, the decision is made to stop study treatment or to continue for an additional 3 months. Regardless of the duration of study treatment (3, 6, 9 or 12 months), an additional 1-month post-treatment observational period will be completed for all children. after cessation of study treatment, it is at the investigator's discretion to continue with anticoagulants. The primary efficacy outcome is symptomatic recurrent venous thromboembolism. The secondary efficacy outcome is the composite of all symptomatic recurrent venous thromboembolism and asymptomatic deterioration in thrombotic burden on repeat imaging. The principal safety outcome is the composite of overt major and clinically relevant nonmajor bleeding. all suspected clinical study outcomes and baseline and repeat thrombosis imaging tests will be assessed by a central independent adjudication committee (CiaC) blinded to treatment allocation. an independent data monitoring committee (DMC) will monitor the children's safety and give recommendations to the steering committee. For all children, visits are scheduled at regular time points (see Table 1-1). Randomized children who have not received the study drug will be seen (visit or phone contact) at the end of the respective study treatment period at month 3. Children who prematurely discontinue study drug will be seen at the end of the intended study treatment period at month 3, 6, 9 or 12. During all contacts, the treatment and clinical course of the child will be evaluated. Children with suspected efficacy or safety outcomes will undergo confirmatory testing as per standard of care. Blood samples for PK/PD will be taken at defined time points.
1. Children aged 6 months to < 18 years with confirmed venous thromboembolism who receive initial treatment with therapeutic dosages of UFH, LMWH or fondaparinux and require anticoagulant therapy for at least 90 days. 2. Informed consent provided and, if applicable, child assent provided
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Ayesha Noor Zia