Individualization of Ganciclovir and Valganciclovir Doses in Renal Transplant Patients for Prophylaxis or Treatment of Cytomegalovirus(CMV)Infection Using Bayesian Prediction.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Area under the concentration time curve (AUC)of ganciclovir in steady state
研究概览
简要总结
The objective of the present study is to optimize intravenous ganciclovir(GCV) and oral valganciclovir (VGCV)doses, advised by the drug exposure, indicated by the area under the concentration time curve (AUC), in renal transplant patients receiving oral VGCV or intravenous GCV for CMV prophylaxis or treatment. The initial doses will be calculated according to population pharmacokinetic model. Subsequent doses will be adjusted according to plasma GCV concentrations, using the Bayesian approach. This method of dose adjustments could lead to increase the percentage of patients achieving a therapeutic exposure.
详细描述
The area under the concentration time curve of serum concentrations of GCV is an indicator of systemic exposure to the drug and is related to the effectiveness and safety. According to the population model developed by our group, less than 16% of patients treated achieve the therapeutic goal of AUC (40 to 50 mcg • h / L) after drug dosing according to summary of product characteristics (SPC). Especially, patients with impaired renal function values (creatinine clearance (CrC)l <30 ml / min) or high (CrCl> 70 ml / min) would be overdosed and underdosed, respectively, with the risk of more adverse effects or therapeutic failure.
Therefore, the individualization of the dosage of GCV, can contribute greatly to achieve optimal exposure to the drug in transplant patients, especially in the cases of extreme values of renal function (CrCl decreased and high). As a consequence, minimize adverse effects, ensure greater efficiency in the target population and reduce associated costs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be 18 or older, weigh more than 34kg and may be of either sex and race.
- •Subjects must be willing to give informed consent (IC) in writing and be able to do and follow the study. If a subject cannot give informed consent in writing , a legal representative could sign in his place.
- •Women of childbearing potential should perform a pregnancy test at the time of entry and accept the use of a medically acceptable contraceptive method during the study.
排除标准
- •Creatinine Clearance (CrCl )<10 mL / min.
- •Subjects may not have a history of type I hypersensitivity or idiosyncratic reactions to drugs ganciclovir/valganciclovir
- •Pregnancy women.
- •Women breast feeding
- •Subjects may not present at time of inclusion any clinically significant disease that could interfere with study evaluations.
- •Previous participation in another clinical trial sponsored by pharmaceutical industry, in which the promoter and the protocol set which should be the treatment for CMV.
研究组 & 干预措施
1.A (Prophylaxis-SPC)
Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
干预措施: Ganciclovir/ Valganciclovir according to SPC (Drug)
1.B (Prophylaxis- PK model)
Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model.
干预措施: Ganciclovir/ Valganciclovir according to PK model (Drug)
2.A (Treatment-SPC)
Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).
干预措施: Ganciclovir/ Valganciclovir according to SPC (Drug)
2.B (Treatment-PK model)
Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model
干预措施: Ganciclovir/ Valganciclovir according to PK model (Drug)
结局指标
主要结局
Area under the concentration time curve (AUC)of ganciclovir in steady state
时间窗: Change from baseline to the end of the treatment, with an expected average of treatment of 4 weeks in treatment and 90 days in prophylaxis patients.
Values of AUC of ganciclovir achieved with each intervention, that is, ganciclovir and valganciclovir dose adjustment according to SPC(specific product characteristics) or PK (pharmacokinetic) model. In each intervention: after starting treatment, change in route of administration, change in renal clearance \>10 mL/min and end of treatment blood sampling for pharmacokinetic analysis will be performed in order to calculate AUC.
次要结局
- CMV viral load measured by quantitative polymerase chain reaction (PCR)(Change from baseline to day 90 of study entry)
- T-cell immune response against CMV infection measured by Enzyme-linked immunosorbent spot (ELISPOT)(Change from baseline to day 20 of treatment)
研究者
Nuria Lloberas
Clinical Investigator of Nephrology Department
Hospital Universitari de Bellvitge