Clinical trial NCT03339661: Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T Cells Immunomonitoring.
Official title: Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Transplant Infection
Keywords: CMV infection
kidney transplant
γδ T cells monitoring
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2017-11-13
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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

Primary outcomes:
measure: Assessment of virological relapse occurence
timeFrame: 12 months after inclusion visit
Secondary outcomes:
measure: Cumulative incidence of clinical recurrence
timeFrame: 12 months after inclusion visit
measure: γδ T cells expansion dynamic
timeFrame: 12 months after the inclusion visit
measure: Cumulative incidence of clinical recurrence at discontinuation of prophylaxis.
timeFrame: 12 months after the inclusion visit
measure: Cumulative incidence of virological recurrence at discontinuation of prophylaxis.
timeFrame: 12 months after inclusion visit
measure: secondary prophylaxis duration
timeFrame: 12 months after inclusion visit
measure: Prophylaxis treatment savings evaluation
timeFrame: 12 months after inclusion visit
measure: Proportion of antiviral resistant infections
timeFrame: 12 months after inclusion visit
measure: GFR average
timeFrame: 12 months after inclusion visit
measure: Compliance rate
timeFrame: 12 months after inclusion visit
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Hôpital Pellegrin - CHU de Bordeaux
city: Lyon
country: France
facility: Hôpital Edouard Herriot - Hospices Civils de Lyon
Study officials:
affiliation: USMR
name: Edouard LHOMME, Dr
role: STUDY_CHAIR
References: