Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 4
- 主要终点
- Assessment of virological relapse occurence
研究概览
简要总结
In kidney transplant patients, CMV infection remains the leading infectious cause of morbidity and mortality. Clinical and virological relapses are common and are involved in chronic graft dysfunction. To date, it is not certain that secondary prophylaxis allows reducing these relapses, although this prophylaxis is part of the current recommendations. Our team has recently shown that the expansion of γδ T cells in peripheral blood during CMV infection was correlated with the absence of virological and clinical relapses. Indeed, the absence of relapse was associated in 94.7% of cases with the presence of γδ T cells expansion while relapses occurred in about 90% of cases in the absence of γδ T cells expansion. These results suggest that the indication and duration of secondary prophylaxis after the curative treatment of CMV infection in kidney transplantation could be guided by the immune surveillance of γδ T cells.
详细描述
The study aim to demonstrate that the expansion of γδ T cells at the end of curative treatment predicts the absence of virological and clinical relapses. This is a pilot study that will be conducted in the transplant center of Bordeaux and Lyon. After the curative treatment of CMV infection until a negative CMV ADNemia, secondary prophylaxis with valganciclovir will be established based on the results of γδ T cells immunomonitoring:
(I) Secondary prophylaxis will not be started in patients with γδ T cell expansion at the end of curative treatment (group 1) (II) Secondary prophylaxis will be initiated in patients who have not γδ T cell expansion and will continue for 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.
The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia, at one year of a first CMV disease, in kidney transplant patients, with secondary prophylaxis based on the monitoring of γδ T cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 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
- •Male or female over 18 years old without weight or ethnicity criteria, kidney transplant.
- •Patient affiliated or beneficiary of a social security scheme.
- •Patient with symptomatic or non-symptomatic CMV infection requiring curative treatment with ganciclovir or valganciclovir.
- •Free, informed and written consent signed by the participant and the investigator (at the latest, on the day of inclusion and before any examination required by the research).
排除标准
- •Resistance documented to antivirals.
- •Hemodialysis patient.
- •Number of polymorphonuclear neutrophils less than 500 / μL and / or number of platelets less than 25,000 / μL, and / or lower hemoglobin 8 g / dL.
- •Contraindication to valganciclovir, including known hypersensitivity to valganciclovir and / or aciclovir and / or valaciclovir or ganciclovir or their excipients, known severe intolerance to valganciclovir or ganciclovir.
- •Women of childbearing age without a negative pregnancy test at baseline and without effective contraception (estrogen-progestin, intrauterine device) throughout the study period and two months after cessation of the follow-up period.
- •Nursing women.
- •Men without mechanical contraception during treatment and for at least 90 days after treatment.
- •Ongoing participation in another clinical trial evaluating a drug. Participation in an observational study will not be considered a contraindication.
- •The patient's foreseeable inability to comply with planned visits in the protocol.
- •Non-negativation of CMV PCR at 8 weeks
研究组 & 干预措施
Group 2B_Proph treatment and no γδ T cells expansion
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated depends on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if no γδ T cell expansion will occur, a secondary prophylaxis will be initiated during 3 months maximum. Patients who still not had γδ T cells expansion during or at the end of secondary prophylaxis will compose the group 2B.
干预措施: Group 2B_Proph treatment and no γδ T cell expansion (Drug)
Group 1_ No proph treatment
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated will depend on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if γδ T cell expansion occurs, no secondary prophylaxis treatment will be introduce, and curative treatment stops.
干预措施: Group 1_No proph treatment (Drug)
Group 2A_Proph treatment and γδ T cells expansion
Patients will receive a curative treatment (ganciclovir or valganciclovir, drug administrated depends on medical opinion) during 2 to 8 weeks. When CMV QNAT becomes regative, if no γδ T cell expansion will occur, a secondary prophylaxis will be initiated during 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A.
干预措施: Group 2A_Proph treatment and γδ T cell expansion (Drug)
结局指标
主要结局
Assessment of virological relapse occurence
时间窗: 12 months after inclusion visit
The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia.
次要结局
- Cumulative incidence of clinical recurrence(12 months after inclusion visit)
- γδ T cells expansion dynamic(12 months after the inclusion visit)
- Cumulative incidence of clinical recurrence at discontinuation of prophylaxis.(12 months after the inclusion visit)
- Cumulative incidence of virological recurrence at discontinuation of prophylaxis.(12 months after inclusion visit)
- secondary prophylaxis duration(12 months after inclusion visit)
- Prophylaxis treatment savings evaluation(12 months after inclusion visit)
- Proportion of antiviral resistant infections(12 months after inclusion visit)
- GFR average(12 months after inclusion visit)
- Compliance rate(12 months after inclusion visit)