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

NCT03339661 | Completed Phase 2

• 2 other identifiers: CHUBX 2016/402017-002912-15
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

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.

Conditions

Kidney Transplant Infection

Keywords

CMV infection; kidney transplant; γδ T cells monitoring

Outcome Measures

Primary Outcomes (1)

• Assessment of virological relapse occurence

  The primary outcome of this study will be to evaluate the occurrence of virological relapse, assessed by monitoring CMV ADNemia.

  12 months after inclusion visit

Secondary Outcomes (9)

• 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

Study Arms (3)

Group 1_ No proph treatment

EXPERIMENTAL

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.

Drug: Group 1_No proph treatment

Group 2A_Proph treatment and γδ T cells expansion

EXPERIMENTAL

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.

Drug: Group 2A_Proph treatment and γδ T cell expansion

Group 2B_Proph treatment and no γδ T cells expansion

EXPERIMENTAL

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.

Drug: Group 2B_Proph treatment and no γδ T cell expansion

Interventions

Group 2B_Proph treatment and no γδ T cell expansion 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.

Group 2B_Proph treatment and no γδ T cells expansion

Group 1_No proph treatment 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 1_ No proph treatment

Group 2A_Proph treatment and γδ T cell expansion 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 2A_Proph treatment and γδ T cells expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (2)

Hôpital Pellegrin - CHU de Bordeaux

Bordeaux, 33000, France

Location

Hôpital Edouard Herriot - Hospices Civils de Lyon

Lyon, 69003, France

Location

MeSH Terms

Conditions

Cytomegalovirus Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Edouard LHOMME, Dr

  USMR

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2017
• First Posted: November 13, 2017
• Study Start: November 23, 2017
• Primary Completion: November 23, 2020
• Study Completion: November 23, 2020
• Last Updated: May 12, 2026

Record last verified: 2021-06

Locations

FR (2)