(Val)Ganciclovir Therapeutic Drug Monitoring in Transplant Recipients
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Failure of CMV treatment (with valganciclovir and ganciclovir) using viral load measurements and determining mutations in CMV kinase gene UL97 and DNA polymerase gene UL54
研究概览
简要总结
The aim of this study is to gain more insight into therapeutic drug monitoring and thus the pharmacodynamics and pharmacokinetics of ganciclovir, in the context of prophylaxis and treatment of CMV infections, in order to provide the patient with an adequate dose.
详细描述
Patients undergoing solid organ or stem cell transplantation are at risk of developing cytomegalovirus (CMV) infection or reactivation. The risk of CMV infection / reactivation and its severity depends on the CMV serostatus of donor and recipient. Valganciclovir (oral pro-drug of ganciclovir) prophylaxis is used to postpone CMV infection or reactivation to a later point in the post-transplantation.
CMV infection/reactivation does not always lead to clinical disease. Valganciclovir (oral) can be used when CMV DNA is detected in the blood, but patient has no or few complaints. However, in case of severe symptoms such as colitis, nephritis, hepatitis, pneumonitis, uveitis or encephalitis (active CMV disease) then ganciclovir is indicated intravenously. In clinical recovery treatment is often completed with valganciclovir.
It is important that the ganciclovir level is adequate, because too high level can lead to side effects such as cytopenia and a too low level can lead to treatment failure and resistance development. There are different dosing schedules mentioned in different sources. These schemes are based on dated literature.
The aim of (val)ganciclovir therapeutic drug monitoring (TDM) is to gain more insight into the pharmacodynamics and pharmacokinetics of ganciclovir, in the context of prophylaxis and treatment of CMV infections, in order to provide the patient with an adequate dose.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
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
- •Must receive ganciclovir intravenously or valganciclovir orally as routine care
- •Must have received a solid organ or stem cell transplant
- •Must be be 18 years or older
排除标准
- •There are no exclusion criteria.
研究组 & 干预措施
Prophylaxis
Patients who receive (val)ganciclovir for prophylaxis of cytomegalovirus
干预措施: Valganciclovir (Drug)
Prophylaxis
Patients who receive (val)ganciclovir for prophylaxis of cytomegalovirus
干预措施: Ganciclovir (Drug)
Treatment
Patients who receive (val)ganciclovir for treatment of cytomegalovirus
干预措施: Ganciclovir (Drug)
Treatment
Patients who receive (val)ganciclovir for treatment of cytomegalovirus
干预措施: Valganciclovir (Drug)
结局指标
主要结局
Failure of CMV treatment (with valganciclovir and ganciclovir) using viral load measurements and determining mutations in CMV kinase gene UL97 and DNA polymerase gene UL54
时间窗: 12 months after transplantation
How many days to the development of failure of treatment? Failure of treatment is defined by increased viral load (measured in serum, whole blood, plasma in copies per mL and/or viral resistance (change of ganciclovir treatment to foscarnet treatment as a consequence, resistance is determined by resistance testing determining CMV kinase gene UL97 and DNA polymerase gene UL54 for mutations) or death due to CMV.
次要结局
- Therapeutic window(12 months after transplantation)
- Breakthrough CMV infection during CMV prophylaxis with valganciclovir(12 months after transplantation)
- Successful treatment while receiving (val)ganciclovir determined by two consequtive negative viral loads(12 months after transplantation)
- (Val)ganciclovir for treatment outcomes (1)(12 months after transplantation)
- (Val)ganciclovir for treatment outcomes (2)(12 months after transplantation)
- Factors that can influence trough concentrations of (val)ganciclovir (1)(12 months after transplantation)
- Factors that can influence trough concentrations of (val)ganciclovir (2)(12 months after transplantation)
- Factors that can influence trough concentrations of (val)ganciclovir (3)(12 months after transplantation)
研究者
Jan-Willem C Alffenaar
Principal Investigator, Clinical pharmacologist
University Medical Center Groningen