Secondary Prophylaxis After CMV Disease in Kidney Transplant Patients Targeted by γδ T Cells Immunomonitoring.

NCT ID: NCT03339661

Last Updated: 2021-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-23
• Study Completion Date: 2020-11-23

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.

Conditions

Kidney Transplant Infection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Group 1_No proph treatment

Intervention Type: DRUG

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. In this group, expansion of γδ T cell at the end curative treatment was detected, so secondary prophylaxis will not be started.

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.

Group Type: EXPERIMENTAL

Group 2A_Proph treatment and γδ T cell expansion

Intervention Type: DRUG

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. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A.

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.

Group Type: EXPERIMENTAL

Group 2B_Proph treatment and no γδ T cell expansion

Intervention Type: DRUG

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. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue 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.

Interventions

Group 1_No proph treatment

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. In this group, expansion of γδ T cell at the end curative treatment was detected, so secondary prophylaxis will not be started.

Intervention Type: DRUG

Group 2A_Proph treatment and γδ T cell expansion

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. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue during 3 months maximum. The occurrence of γδ T cells expansion during or at the end of secondary prophylaxis will define the group 2A.

Intervention Type: DRUG

Group 2B_Proph treatment and no γδ T cell expansion

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. In this group, γδ T cell expansion will not be detected, so secondary prophylaxis will be initiated in continue 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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Edouard LHOMME, Dr

Role: STUDY_CHAIR

USMR

Locations

Hôpital Pellegrin - CHU de Bordeaux

Bordeaux, , France

Hôpital Edouard Herriot - Hospices Civils de Lyon

Lyon, , France

Countries

France

Other Identifiers

CHUBX 2016/40

Identifier Type: -

Identifier Source: org_study_id