UNBLOCK: an open‐label, dose‐finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis. (6th August 2015)

• Record Type: Journal Article
• Authors: O'Brien, S. H.; Yee, D. L.; Lira, J.; Goldenberg, N. A.; Young, G.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 9(2015:Sep.)
• Page Start: 1615
• Page End: 1622
• Publication Date: 2015-08-06
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13057
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth13057-abs-0001"> <title>Summary</title> <sec id="jth13057-sec-0001" sec-type="section"> <title>Background</title> <p>Direct thrombin inhibitors offer potential advantages over unfractionated heparin but have been poorly studied in children.</p> </sec> <sec id="jth13057-sec-0002" sec-type="section"> <title>Objectives</title> <p>To determine appropriate dosing of bivalirudin in children and adolescents and the relationship between activated partial thromboplastin time (APTT) and plasma bivalirudin concentration.</p> </sec> <sec id="jth13057-sec-0003" sec-type="section"> <title>Patients/Methods</title> <p>The UNBLOCK (UtilizatioN of BivaLirudin On Clots in Kids) study was an open‐label, single‐arm, dose‐finding, pharmacokinetic, safety and efficacy study of bivalirudin for the acute treatment of deep vein thrombosis (DVT) in children aged 6 months to 18 years. Drug initiation consisted of a bolus dose (0.125 mg kg<sup>−1</sup>) followed by continuous infusion (0.125 mg kg h<sup>−1</sup>). Dose adjustments were based on the APTT, targeting a range of 1.5–2.5 times each patient's baseline APTT. Safety was assessed by specific bleeding endpoints and efficacy by repeat imaging at 48–72 h and 25–35 days.</p> </sec> <sec id="jth13057-sec-0004" sec-type="section"> <title>Results</title> <p>Eighteen patients completed the study. Following the bolus dose and the initial infusion rate, most patients' APTT values were within the target range. The infusion rate bivalirudin correlated more closely with drug concentration than the APTT. At 48–72 h, nine (50%) patients had complete or partial thrombus resolution, increasing to 16 (89%) at 25–35 days. No major and one minor bleeding event occurred.</p> </sec> <sec id="jth13057-sec-0005" sec-type="section"> <title>Conclusions</title> <p>Bivalirudin demonstrated reassuring safety and noteworthy efficacy in terms of early clot resolution in children and adolescents with DVT. Although a widely available and familiar monitoring tool, the APTT correlates poorly with plasma bivalirudin concentration, possibly limiting its utility in managing pediatric patients receiving bivalirudin for DVT.</p> </sec> </abstract>