Multicentre, Open Study for the Setting up of Population Pharmacokinetic Models and Bayesian Estimators for Individual Dose Adjustment of Immunosuppressive Drugs (Cyclosporine, Tacrolimus, Mycophenolate Mofetil, Everolimus) During the First Year Post-grafting in Adult Heart Transplant Recipients.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 12
- 主要终点
- Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.
研究概览
简要总结
The main objective is to develop pharmacokinetic methods for individual dose adjustment of the global immunosuppressive treatment (cyclosporine, tacrolimus, mycophenolate mofetil and everolimus, taking into account the pharmacokinetic interactions), in order to optimise the efficiency and reduce the potentially severe sides effects of these drugs.
Forty five heart-transplant patients are to be included in this phase IV study to obtain a minimum of 10 patients treated with tacrolimus-mycophenolate, 10 with cyclosporine-mycophenolate and 20 with everolimus-cyclosporine.
Ten to 11 blood samples will be collected within the 8 to 12 hours post-dose in each patient and the immunosuppressive drug concentrations will be measured by LC-MS/MS.
The pharmacokinetic models and Bayesian estimators thus developed will provide tools for individual dose adjustment of immunosuppressive drugs simultaneously, at different post-transplant periods, using the area under the concentration-time curve (AUC) estimated using a limited number of time-points (2 or 3).
详细描述
For each heart transplant patient, 10 to 11 blood samples (5 mL each) will be collected following dosing of he immunosuppressive drugs (at T0, T20', T40', T60', T90', T2h, T3h, T4h, T6h, T8h and T10h + T12h for inpatients), at several post-transplant periods (7 to 15 days, 1 month, 3 month and 1 year after transplantation). One more blood sample will be taken at D7-14 for pharmacogenetic analyses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient having received of a heart transplant (exclusively) less than 2 weeks before the inclusion date or planned to receive it within days following inclusion.
- •Patient at least 18 years old, male or female.
- •Patient treated with one of the following combination : cyclosporine-mycophenolate, tacrolimus-mycophenolate or everolimus- "low-dose" cyclosporine for at least 3 days, and at least 24 hours by the oral route at the time of the first sampling day (between 7 and 15 days post-transplant).
- •Patient included or not in another study, in particular in a therapeutic trial (e.g. comparison between drug combinations).
- •Patient having given written informed consent for his/her participation to the trial.
排除标准
- •Patients in disagreement with the present trial.
- •Patients suffering from neuro-psychic problems, making them unable to well-understand the protocol or to give a reliable consent.
- •Patients with previous heart or any other solid organ transplantation.
- •Patients with double transplantation (heart-lung, heart-kidney or heart-liver)
- •Patients still intubated and ventilated 15 days post-transplant.
- •Patients with anaemia between Day 7 and 15, as characterized by hematocrit < 30% or haemoglobin < 9 g/dl.
结局指标
主要结局
Estimation of the pharmacokinetic properties and parameters of the immunosuppressive drugs.
次要结局
- Investigation of relationships between physiological and pathological characteristics and individual pharmacokinetic parameters.
- Characterisation of the exposure-clinical effects relationships for the difference immunosuppressive drugs.