An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.
ABSTRACT Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children.
This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely.
At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group.
Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.
Article: Long-term safety and efficacy data on childhood venous thrombosis treated with a low molecular weight heparin: an open-label pilot study of once-daily versus twice-daily enoxaparin administration.[show abstract] [hide abstract]
ABSTRACT: In this open label pilot safety study 80 children over 3 months old with deep venous thrombosis were treated with enoxaparin with a target 4 h anti-factor Xa activity between 0.5-0.8 IU/mL. The children were stratified to receive once daily or twice daily doses. The study end-points were post-thrombotic syndrome, re-thrombosis, bleeding, and therapy-related death. The median duration of treatment was 5 months and the median follow-up was 24 months. No significant differences were found between the two groups of patients. No bleeding or therapy-related deaths occurred. These safety and efficacy data may serve as a basis to initiate an international multicenter study on enoxaparin treatment.Haematologica 01/2007; 91(12):1701-4. · 6.42 Impact Factor
Article: Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: a cochrane systematic review.[show abstract] [hide abstract]
ABSTRACT: Cancer and its therapies increase the risk of venous thromboembolism. Compared to patients without cancer, patients with cancer anticoagulated for venous thromboembolism are more likely to develop recurrent thrombotic events and major bleeding. Addressing all important outcomes including harm is of great importance to make evidence based health care decisions. The objective of this study was to compare low molecular weight heparin (LMWH) and oral anticoagulants (vitamin K antagonist (VKA) and ximelagatran) for the long term treatment of venous thromboembolism in patients with cancer. A systematic review of the medical literature. We followed the Cochrane Collaboration methodology for conducting systematic reviews. We assessed methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Eight randomized controlled trials (RCTs) were eligible and reported data for patients with cancer. The quality of evidence was low for death and moderate for recurrent venous thromboembolism. LMWH, compared to VKA provided no statistically significant survival benefit (Hazard ratio (HR) = 0.96; 95% CI 0.81 to 1.14) but a statistically significant reduction in venous thromboembolism (HR = 0.47; 95% (Confidence Interval (CI) = 0.32 to 0.71). There was no statistically significant difference between LMWH and VKA in bleeding outcomes (RR = 0.91; 95% CI = 0.64 to 1.31) or thrombocytopenia (RR = 1.02; 95% CI = 0.60 to 1.74). For the long term treatment of venous thromboembolism in patients with cancer, LMWH compared to VKA reduces venous thromboembolism but not death.Journal of Experimental & Clinical Cancer Research 01/2008; 27:21. · 2.15 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Pulmonary embolism is an uncommon, but potentially fatal disease in children. Most children with pulmonary embolism have underlying clinical conditions, of which the presence of a central venous catheter is the most frequent. The clinical presentation is often subtle, or masked by the underlying clinical condition. Diagnostic as well as therapeutic strategies for pulmonary embolism in children are mostly extrapolated from studies in adults. Pulmonary angiography is still the gold standard in diagnosing pulmonary embolism, but several other radiographic tests can be used to diagnose pulmonary embolism, including ventilation-perfusion lung scanning, helical computed tomography, magnetic resonance imaging and echocardiography. The choice of treatment depends on the clinical presentation of the patient. Anticoagulation is the mainstay of therapy for children with pulmonary embolism. However, thrombolytic therapy can be considered for patients with hemodynamic instability. The outcome of pediatric pulmonary embolism is uncertain and needs to be studied.Thrombosis Research 02/2006; 118(1):13-25. · 2.44 Impact Factor