Valganciclovir Dosing in Pediatric Solid Organ Transplant Recipients - a Prospective Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Area Under the Curve (AUC)
研究概览
简要总结
Valganciclovir is extensively used for cytomegalovirus (CMV) infection treatment and prophylaxis after solid organ transplantation (SOT). VGC dosing is problematic in children. valganciclovir has variable absorption and is renally excreted. Area Under the Curve (AUC) (0-24) of 40-60 mcg∙h/L is a predictive pharmacokinetic parameter of efficacy and safety. Dosing based on manufacturer recommendations is supra-therapeutic in most cases. A few published dosing algorithms result in AUC out of range.
Objective: To prospectively validate a Valganciclovir administration dosing regimen and compare it to other dosing algorithms.
Methods: Children after SOT at Schneider Children's Medical Center, the largest tertiary pediatric center in Israel, were prospectively studied, starting Dec 2014. The dosing regimen was derived from Seattle Children's Hospital guidelines; 14-16 mg/kg/dose. For impaired renal function, stratified dose reduction was used. Blood was withdrawn at steady state: 2, 5 and 10 hours post dosing. Drug level was analyzed by high pressure liquid chromatography (HPLC).
详细描述
Valganciclovir is a novel drug used extensively as a prophylactic, preemptive and treatment agent for cytomegalovirus (CMV) infection after solid organ transplantation (SOT).
It is the valine ester prodrug of Ganciclovir,has a bioavailability of approximately 60%, which is up to 10-fold higher than oral ganciclovir .
Based on the correlation between the Pharmacokinetic (PK) of VGC and its clinical efficacy found in adult studies, AUC (0-24) of approximately 40-60 mcg∙h/mL has been described as predictive PK parameter of efficacy. Considering the mechanism of action of Valganciclovir , relationships of exposure-efficacy and exposure-safety are expected to be similar in children and adults.
In 2009, a new dosing algorithm incorporating both body surface area (BSA) and renal function was introduced by the manufacturer for infants and young children:
Dose (mg) =7 × BSA × CrCl
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •children and adolescents 0-18 years old
- •Solid Organ Transplantation admitted after transplantation
- •Treatment with prophylactic Valganciclovir
- •Glomerular Filtration Rate (GFR) >= 60 mL/min/1.73 m2
排除标准
- •Treatment with ganciclovir IV
- •Glomerular Filtration Rate (GFR) < 60 mL/min/1.73 m2
- •Imipenem treatment
- •Cluster organ transplanted -
研究组 & 干预措施
Solid Organ Transplanted children
Intervention: treatment with prophylactic oral valganciclovir with a fixed dose of 17 mg/kg once daily for prophylaxis, and stratified dose reductions for impaired renal function. Max dose was 900 mg.
干预措施: prophylactic Valganciclovir (Drug)
结局指标
主要结局
Area Under the Curve (AUC)
时间窗: drug levels measured at 2, 5 and 10 h following administration of the dose on day 4 creating a 24 hours curve
Valganciclovir area under the curve (AUC) calculated with the trapezoidal method using drug levels measured at 2, 5 and 10 h, and extrapolated beyond the 10 hour time point to arrive at a 24-hour curve.
次要结局
未报告次要终点