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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Massicotte
Patricia
P
Division of Hematology/Oncology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. patricia.massicotte@sickkids.ca
Julian
Jim A
JA
Gent
Michael
M
Shields
Karen
K
Marzinotto
Velma
V
Szechtman
Barbara
B
Andrew
Maureen
M
D000284:Administration, Oral; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D006493:Heparin / Q000008:administration & dosage*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007391:International Cooperation; D011655:Pulmonary Embolism / Q000188:drug therapy*; D013923:Thromboembolism / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000379:methods; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000188:drug therapy*; D014859:Warfarin / Q000008:administration & dosage*
D006495:Heparin, Low-Molecular-Weight; D014859:Warfarin; C094240:reviparin; D006493:Heparin